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Volume 30,Issue 12,2023 Table of Contents
2023, 30(12):1035-1042.
DOI: 10.3872/j.issn.1007-385X.2023.12.001
Abstract:
N7-methylguanosine (m7G) is one of the most common RNA modifications in epigenetic regulation, it plays an important role in the processing and metabolism of a variety of RNA molecules such as messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and microRNAs, and thus participates in many cellular processes such as cell proliferation, differentiation, apoptosis and migration. Increasing evidence suggests that m7G methylation is involved in tumorigenesis and tumor development. The abnormal m7G methylation is closely related to tumor development and progression by regulating the expression of multiple oncogenes and tumor suppressor genes, to promote or inhibit, the progression of various types of tumors. Molecules modified by m7G methylation and their regulators can be potential targets for tumor diagnosis and therapy. In this article, the recent advances in m7G modifications, the detection methods of m7G modification and the potential molecular mechanisms of the role of m7G modification in tumorigenesis and tumor development cancer are reviewed.
N7-methylguanosine (m7G) is one of the most common RNA modifications in epigenetic regulation, it plays an important role in the processing and metabolism of a variety of RNA molecules such as messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs) and microRNAs, and thus participates in many cellular processes such as cell proliferation, differentiation, apoptosis and migration. Increasing evidence suggests that m7G methylation is involved in tumorigenesis and tumor development. The abnormal m7G methylation is closely related to tumor development and progression by regulating the expression of multiple oncogenes and tumor suppressor genes, to promote or inhibit, the progression of various types of tumors. Molecules modified by m7G methylation and their regulators can be potential targets for tumor diagnosis and therapy. In this article, the recent advances in m7G modifications, the detection methods of m7G modification and the potential molecular mechanisms of the role of m7G modification in tumorigenesis and tumor development cancer are reviewed.
2023, 30(12):1043-1050.
DOI: 10.3872/j.issn.1007-385X.2023.12.002
Abstract:
Objective: To construct a cyclic arginine-glycine-aspartate (cRGD)-modified, Zn2+-doped and disulfiram-loaded dendritic mesoporous silicon nanoparticles and to preliminarily investigate its targeting and killing effects against colorectal cancer CT26 cells.Methods: Firstly, Zn2+ was anchored in the skeleton of dendritic mesoporous silicon nanoparticles by hydrothermal synthesis method,then disulfiram was loaded into the pores, and the targeting ligand cRGD was coupled to the surface of the nanoparticles to obtain functional nanoparticles DSF@Zn-DMSN-cRGD. After that, transmission electron microscopy (TEM) was used to detect the surface morphology of DSF@Zn-DMSN-cRGD, and energy spectrum scanning was further used to obtain element mapping images to verify element distribution. Laser particle size analyzer was used to detect the changes of particle size and zeta potential, and infrared spectrometer was used to detect the major chemical bonds on the surface. The morphology of carrier Zn-DMSN after being co-cultured in simulated body fluid solution (pH6.5 and pH7.4) was observed by transmission electron microscopy. Cell uptake assay was used to detect the ability of cRGD-modified Zn-DMSN to target CT26 cells. CCK-8 assay, Calcein-AM/PI staining and flow cytometry were used to detected the killing ability of DSF@Zn-DMSN-cRGD against CT26 cells and its influence on the apoptosis of CT26 cells.Results: The TEM image displayed that the surface of DSF@Zn-DMSN-cRGD was a multi-aperture structure. Element mapping images showed Zn and DSF were successfully loaded on the surface of nanoparticles. The results of infrared spectroscopy showed that cRGD was successfully coupled on the surface of DSF@Zn-DMSN. The particle size slightly increased after coupling cRGD, while the zeta potential obviously increased (P<0.000 1). The images of TEM showed that Zn-DMSN disintegrated faster in pH6.5 solution than in pH7.4 solution. The results of cell uptake experiments showed that the efficiency of CT26 cells uptaking cRGD-modified Zn-DMSN was enhanced prominently (P<0.05). After DSF@Zn-DMSN-cRGD treatment, the results of CCK-8 assay, Calcein-AM/PI staining,and flow cytometry showed that DSF@Zn-DMSN-cRGD could efficiently kill CT26 cells (all P<0.000 1) and induce apoptosis (all P<0.000 1); there was no significant damage to normal colon epithelial cells. Conclusion: DSF@Zn-DMSN-cRGD has been successfully synthesized, and its core skeleton of carrier Zn-DMSN respondes well to pH degradation. In vitro, DSF@Zn-DMSN-cRGD shows substantial targeted toxicity against colorectal cancer cell line CT26, among them, cRGD promotes the targeted endocytosis of nanoparticles by CT26 cells.
Objective: To construct a cyclic arginine-glycine-aspartate (cRGD)-modified, Zn2+-doped and disulfiram-loaded dendritic mesoporous silicon nanoparticles and to preliminarily investigate its targeting and killing effects against colorectal cancer CT26 cells.Methods: Firstly, Zn2+ was anchored in the skeleton of dendritic mesoporous silicon nanoparticles by hydrothermal synthesis method,then disulfiram was loaded into the pores, and the targeting ligand cRGD was coupled to the surface of the nanoparticles to obtain functional nanoparticles DSF@Zn-DMSN-cRGD. After that, transmission electron microscopy (TEM) was used to detect the surface morphology of DSF@Zn-DMSN-cRGD, and energy spectrum scanning was further used to obtain element mapping images to verify element distribution. Laser particle size analyzer was used to detect the changes of particle size and zeta potential, and infrared spectrometer was used to detect the major chemical bonds on the surface. The morphology of carrier Zn-DMSN after being co-cultured in simulated body fluid solution (pH6.5 and pH7.4) was observed by transmission electron microscopy. Cell uptake assay was used to detect the ability of cRGD-modified Zn-DMSN to target CT26 cells. CCK-8 assay, Calcein-AM/PI staining and flow cytometry were used to detected the killing ability of DSF@Zn-DMSN-cRGD against CT26 cells and its influence on the apoptosis of CT26 cells.Results: The TEM image displayed that the surface of DSF@Zn-DMSN-cRGD was a multi-aperture structure. Element mapping images showed Zn and DSF were successfully loaded on the surface of nanoparticles. The results of infrared spectroscopy showed that cRGD was successfully coupled on the surface of DSF@Zn-DMSN. The particle size slightly increased after coupling cRGD, while the zeta potential obviously increased (P<0.000 1). The images of TEM showed that Zn-DMSN disintegrated faster in pH6.5 solution than in pH7.4 solution. The results of cell uptake experiments showed that the efficiency of CT26 cells uptaking cRGD-modified Zn-DMSN was enhanced prominently (P<0.05). After DSF@Zn-DMSN-cRGD treatment, the results of CCK-8 assay, Calcein-AM/PI staining,and flow cytometry showed that DSF@Zn-DMSN-cRGD could efficiently kill CT26 cells (all P<0.000 1) and induce apoptosis (all P<0.000 1); there was no significant damage to normal colon epithelial cells. Conclusion: DSF@Zn-DMSN-cRGD has been successfully synthesized, and its core skeleton of carrier Zn-DMSN respondes well to pH degradation. In vitro, DSF@Zn-DMSN-cRGD shows substantial targeted toxicity against colorectal cancer cell line CT26, among them, cRGD promotes the targeted endocytosis of nanoparticles by CT26 cells.
2023, 30(12):1051-1060.
DOI: 10.3872/j.issn.1007-385X.2023.12.003
Abstract:
Objective: To explore the molecular mechanism by which methyltransferase-like protein 3 (METTL3) -modified RNASEH1-AS1 regulates the malignant biological behaviors of colorectal cancer cells SW480 through the BUD13/membrane associated protein A2/Wnt/β-catenin (BUD13/ANXA2/Wnt/β-catenin) axis. Methods: Twenty-four CRC patients who were surgically treated in our hospital from June 2022 to November 2022 were selected as the study subjects, and the patients' CRC tissues and corresponding paracancerous tissues were collected, and the qPCR method was used to detect the METTL3, RNASEH1-AS1, BUD13,ANXA2, β -catenin, GSK-3β mRNA in CRC tissues and paracancerous tissues expression, and the correlation of RNASEH1-AS1 expression with METTL3 expression and BUD13 expression in CRC tissues was analyzed by Pearson's method. Colorectal cancer cells SW480 were routinely cultured, and the experiments were divided into sh-NC group, sh-RNASEH1-AS1 group, NC group, sh-METTL group, si-NC group, si-BUD13 group, sh-RNASEH1-AS1+pc-NC group, sh-RNASEH1-AS1+pc-ANXA2 group, sh-METTL+pc-NC group, sh-METTL+pc-ASEH1-AS1 group, and sh-NC, sh-RNASEH1-AS1, sh-NC, sh-METTL, si-NC, si-BUD13, sh-RNASEH1-AS1 and pc-NC, sh-RNASEH1-AS1 and pc- ANXA2, sh-METTL and pc-NC, sh-METTL and pc-ASEH1-AS1 were transfected in SW480 cells. The expression of METTL3, RNASEH1-AS1, BUD13, and ANXA2 in SW480 cells was detected by qPCR. The cell clone formation assay detected the proliferative ability of SW480 cells in the transfected groups; FCM assay detected the apoptosis of SW480 cells in the transfected groups; cell scratch assay detected the migratory ability of SW480 cells in the transfected groups; and WB assay detected the migration of SW480 cells in the transfected groups. ANXA2, β-catenin, p-β-catenin, GSK-3β, p-GSK-3β, c-Myc, cyclinD1 protein expression in each group of SW480 cells; RNA immunoprecipitation (RIP) assay to detect the targeting relationship between RNASEH1-AS1 and BUD1, and BUD1 and ANXA2. Results: Both database analysis and qPCR assay results of CRC tissues and cancerous tissues of nationals showed that METTL3, RNASEH1-AS1, BUD13, ANXA2, β -catenin, and GSK-3β were significantly highly expressed in CRC tissues compared with paracancerous tissues (all P<0.01), and RNASEH1-AS1 expression was positively correlated with the METTL3 (r=0.698, P<0.01) and BUD13 (r=0.784, P<0.01) expression were positively correlated. METTL3, RNASEH1-AS1, BUD13, and ANXA2 mRNA were highly expressed in colon cancer cells (all P<0.05), and the expression of RNASEH1-AS1, BUD13, and ANXA2 was significantly decreased in SW480 cells after knockdown of RNASEH1-AS1 or METTL3 (all P<0.05), while overexpression of RNASEH1-AS1 significantly upregulated the expression of the above molecules (all P<0.05).Knockdown of RNASEH1-AS1 or METTL3 inhibited the proliferation, migration and expression of p-β-catenin, p-GSK-3β, c-Myc,cyclinD1 proteins, and promoted apoptosis of SW480 (all P<0.05), whereas over-expression of RNASEH1-AS1 promoted the proliferation, migration and expression of p-β-catenin p-β-catenin, p-GSK-3β, c-Myc, cyclinD1 protein expression and inhibited its apoptosis (all P<0.05). RNASEH1-AS1 promoted the expression of ANXA2 by recruiting BUD13 targeting (all P<0.05); over-expression of ANXA2 partially reversed the knockdown of the effect of RNASEH1-AS1 on SW480 cells (all P<0.05). Conclusion: METTL3-modified RNASEH1-AS1 regulates the malignant biological behavior of SW480 cells through the BUD13/ANXA2/Wnt/β-catenin axis.
Objective: To explore the molecular mechanism by which methyltransferase-like protein 3 (METTL3) -modified RNASEH1-AS1 regulates the malignant biological behaviors of colorectal cancer cells SW480 through the BUD13/membrane associated protein A2/Wnt/β-catenin (BUD13/ANXA2/Wnt/β-catenin) axis. Methods: Twenty-four CRC patients who were surgically treated in our hospital from June 2022 to November 2022 were selected as the study subjects, and the patients' CRC tissues and corresponding paracancerous tissues were collected, and the qPCR method was used to detect the METTL3, RNASEH1-AS1, BUD13,ANXA2, β -catenin, GSK-3β mRNA in CRC tissues and paracancerous tissues expression, and the correlation of RNASEH1-AS1 expression with METTL3 expression and BUD13 expression in CRC tissues was analyzed by Pearson's method. Colorectal cancer cells SW480 were routinely cultured, and the experiments were divided into sh-NC group, sh-RNASEH1-AS1 group, NC group, sh-METTL group, si-NC group, si-BUD13 group, sh-RNASEH1-AS1+pc-NC group, sh-RNASEH1-AS1+pc-ANXA2 group, sh-METTL+pc-NC group, sh-METTL+pc-ASEH1-AS1 group, and sh-NC, sh-RNASEH1-AS1, sh-NC, sh-METTL, si-NC, si-BUD13, sh-RNASEH1-AS1 and pc-NC, sh-RNASEH1-AS1 and pc- ANXA2, sh-METTL and pc-NC, sh-METTL and pc-ASEH1-AS1 were transfected in SW480 cells. The expression of METTL3, RNASEH1-AS1, BUD13, and ANXA2 in SW480 cells was detected by qPCR. The cell clone formation assay detected the proliferative ability of SW480 cells in the transfected groups; FCM assay detected the apoptosis of SW480 cells in the transfected groups; cell scratch assay detected the migratory ability of SW480 cells in the transfected groups; and WB assay detected the migration of SW480 cells in the transfected groups. ANXA2, β-catenin, p-β-catenin, GSK-3β, p-GSK-3β, c-Myc, cyclinD1 protein expression in each group of SW480 cells; RNA immunoprecipitation (RIP) assay to detect the targeting relationship between RNASEH1-AS1 and BUD1, and BUD1 and ANXA2. Results: Both database analysis and qPCR assay results of CRC tissues and cancerous tissues of nationals showed that METTL3, RNASEH1-AS1, BUD13, ANXA2, β -catenin, and GSK-3β were significantly highly expressed in CRC tissues compared with paracancerous tissues (all P<0.01), and RNASEH1-AS1 expression was positively correlated with the METTL3 (r=0.698, P<0.01) and BUD13 (r=0.784, P<0.01) expression were positively correlated. METTL3, RNASEH1-AS1, BUD13, and ANXA2 mRNA were highly expressed in colon cancer cells (all P<0.05), and the expression of RNASEH1-AS1, BUD13, and ANXA2 was significantly decreased in SW480 cells after knockdown of RNASEH1-AS1 or METTL3 (all P<0.05), while overexpression of RNASEH1-AS1 significantly upregulated the expression of the above molecules (all P<0.05).Knockdown of RNASEH1-AS1 or METTL3 inhibited the proliferation, migration and expression of p-β-catenin, p-GSK-3β, c-Myc,cyclinD1 proteins, and promoted apoptosis of SW480 (all P<0.05), whereas over-expression of RNASEH1-AS1 promoted the proliferation, migration and expression of p-β-catenin p-β-catenin, p-GSK-3β, c-Myc, cyclinD1 protein expression and inhibited its apoptosis (all P<0.05). RNASEH1-AS1 promoted the expression of ANXA2 by recruiting BUD13 targeting (all P<0.05); over-expression of ANXA2 partially reversed the knockdown of the effect of RNASEH1-AS1 on SW480 cells (all P<0.05). Conclusion: METTL3-modified RNASEH1-AS1 regulates the malignant biological behavior of SW480 cells through the BUD13/ANXA2/Wnt/β-catenin axis.
2023, 30(12):1061-1065.
DOI: 10.3872/j.issn.1007-385X.2023.12.004
Abstract:
Objective: To investigate the inhibitory effect of Licochalcone B (LCB) on a triple-negative breast cancer cell line MDA-MB-231 cells and its mechanism. Methods: MDA-MB-231 cells were routinely cultured and treated with different concentrations of LCB, and then CCK-8 assay, immunofluorescence, FCM and WB analysis were used to detect the proliferative viability of MDA-MB-231 cells, the expression of γ-H2AX, a marker of DNA double-strand breaks in the nucleus, the cell cycle，and the expression levels of proteins related to cycle regulation, mitogen-activated protein kinase (MAPK), and the endoplasmic reticulum stress (ER stress),respectively. Results: LCB significantly inhibited the proliferative viability of breast cancer MDA-MB-231 cells (all P<0.05), the number of γ-H2AX-positive cells and protein expression levels were significantly increased after LCB treatment (all P<0.05), the number of cells in G2/M and S phases was significantly increased (all P<0.05), the phosphorylation levels of the main members of the MAPK family,extracellular regulated kinase 1/2 (ERK1/2) and p38 MAPK phosphorylation levels were significantly upregulated (all P<0.05), and the expression of ER stress pathway-related proteins Bip, ATF4 and CHOP were significantly upregulated (all P<0.05). Conclusion: LCB could significantly inhibit the proliferation vitality of MDA-MB-231 cells and induce DNA damage and cell cycle arrest at G2/M and S phases.The inhibitory effect of LCB on MDA-MB-231 cells may be related to the activation of MAPK and ER stress signaling pathway.
Objective: To investigate the inhibitory effect of Licochalcone B (LCB) on a triple-negative breast cancer cell line MDA-MB-231 cells and its mechanism. Methods: MDA-MB-231 cells were routinely cultured and treated with different concentrations of LCB, and then CCK-8 assay, immunofluorescence, FCM and WB analysis were used to detect the proliferative viability of MDA-MB-231 cells, the expression of γ-H2AX, a marker of DNA double-strand breaks in the nucleus, the cell cycle，and the expression levels of proteins related to cycle regulation, mitogen-activated protein kinase (MAPK), and the endoplasmic reticulum stress (ER stress),respectively. Results: LCB significantly inhibited the proliferative viability of breast cancer MDA-MB-231 cells (all P<0.05), the number of γ-H2AX-positive cells and protein expression levels were significantly increased after LCB treatment (all P<0.05), the number of cells in G2/M and S phases was significantly increased (all P<0.05), the phosphorylation levels of the main members of the MAPK family,extracellular regulated kinase 1/2 (ERK1/2) and p38 MAPK phosphorylation levels were significantly upregulated (all P<0.05), and the expression of ER stress pathway-related proteins Bip, ATF4 and CHOP were significantly upregulated (all P<0.05). Conclusion: LCB could significantly inhibit the proliferation vitality of MDA-MB-231 cells and induce DNA damage and cell cycle arrest at G2/M and S phases.The inhibitory effect of LCB on MDA-MB-231 cells may be related to the activation of MAPK and ER stress signaling pathway.
ZHANG Bochao
,
MA Siyuan
,
ZHU Ping
,
ZHAO Xiaoxiao
,
WANG Cheng
,
LIU Jingwen
,
JIANG Ping
,
PU Chun
2023, 30(12):1066-1073.
DOI: 10.3872/j.issn.1007-385X.2023.12.005
Abstract:
Objective: To investigate the effect of miR-4465 targeting high mobility group protein A1 (HMGA1) on the proliferation, migration and invasion of hepatocellular carcinoma Hep3B cells. Methods: Sixteen pairs of cancer tissues and adjacent tissue samples from patients diagnosed with hepatocellular carcinoma in the First Affiliated Hospital of Wannan Medical College from May 2020 to September 2021 were collected. The expression of miR-4465 in hepatocellular carcinoma tissues and Hep3B and Huh7 cells was analyzed by qPCR, and the regulatory relationship between miR-4465 and HMGA1 was verified by dual luciferase reporter gene assay. According to the different transfections, Hep3B cells were group, si-NC group, and si-HMGA1 group for transfection; in addition, mimics-NC+pcDNA-NC, miR-4465 mimics+pcDNA-NC, and miR-4465 mimics+pcDNA-HMGA1 were transfected for rescue experiments. The changes of mRNA and protein levels of HMGA1 in each group were detected by qPCR and WB assay; the changes in cell proliferation activity in each group were detected by CCK-8 method; the changes in cell migration ability in each group were detected by scratch assay, and the changes in cell invasion ability in each group were detected by Transwell assay. Results: The expression of miR-4465 in hepatocellular carcinoma tissues and cells was significantly lower than that in adjacent tissues and normal liver cells (P<0.05 or P<0.001). After transfection for 48 h, the proliferation, migration and invasion abilities of Hep3B cells overexpressing miR-4465 were significantly decreased (P<0.05, P<0.01 or P<0.001); the proliferation, migration and invasion abilities of Hep3B cells with miR-4465 knockdown were increased (P<0.05, P<0.01 or P<0.001). The binding relationship between HMGA1-3'UTR and miR-4465 was verified by dual luciferase report gene experiment. miR-4465 could target and down-regulate the mRNA and protein expression of HMGA1 (all P<0.01). Over-expression of HMGA1 partially restored the inhibitory effects of miR-4465 overexpression on cell proliferation, migration and invasion as well as HMGA1 expression (all P<0.05). Conclusion: miR-4465 inhibits the malignant biological behaviors of hepatocellular carcinoma Hep3B cells by down-regulating the expression of HMGA1 in the cells.
Objective: To investigate the effect of miR-4465 targeting high mobility group protein A1 (HMGA1) on the proliferation, migration and invasion of hepatocellular carcinoma Hep3B cells. Methods: Sixteen pairs of cancer tissues and adjacent tissue samples from patients diagnosed with hepatocellular carcinoma in the First Affiliated Hospital of Wannan Medical College from May 2020 to September 2021 were collected. The expression of miR-4465 in hepatocellular carcinoma tissues and Hep3B and Huh7 cells was analyzed by qPCR, and the regulatory relationship between miR-4465 and HMGA1 was verified by dual luciferase reporter gene assay. According to the different transfections, Hep3B cells were group, si-NC group, and si-HMGA1 group for transfection; in addition, mimics-NC+pcDNA-NC, miR-4465 mimics+pcDNA-NC, and miR-4465 mimics+pcDNA-HMGA1 were transfected for rescue experiments. The changes of mRNA and protein levels of HMGA1 in each group were detected by qPCR and WB assay; the changes in cell proliferation activity in each group were detected by CCK-8 method; the changes in cell migration ability in each group were detected by scratch assay, and the changes in cell invasion ability in each group were detected by Transwell assay. Results: The expression of miR-4465 in hepatocellular carcinoma tissues and cells was significantly lower than that in adjacent tissues and normal liver cells (P<0.05 or P<0.001). After transfection for 48 h, the proliferation, migration and invasion abilities of Hep3B cells overexpressing miR-4465 were significantly decreased (P<0.05, P<0.01 or P<0.001); the proliferation, migration and invasion abilities of Hep3B cells with miR-4465 knockdown were increased (P<0.05, P<0.01 or P<0.001). The binding relationship between HMGA1-3'UTR and miR-4465 was verified by dual luciferase report gene experiment. miR-4465 could target and down-regulate the mRNA and protein expression of HMGA1 (all P<0.01). Over-expression of HMGA1 partially restored the inhibitory effects of miR-4465 overexpression on cell proliferation, migration and invasion as well as HMGA1 expression (all P<0.05). Conclusion: miR-4465 inhibits the malignant biological behaviors of hepatocellular carcinoma Hep3B cells by down-regulating the expression of HMGA1 in the cells.
2023, 30(12):1074-1081.
DOI: 10.3872/j.issn.1007-385X.2023.12.006
Abstract:
Objective: To investigate the expression of SNRPA in hepatocellular carcinoma (HCC) and cells and the role and mechanism of small nuclear ribonucleoprotein polypeptide A (SNRPA) in regulating the malignant biological behaviors of HCC HepG2 and Hep3B cells. Methods: The database was used to analyze the expression of SNRPA in pan-cancer tissues and its correlation with the pathological stage and the prognosis of HCC patients. HepG2 and Hep3B cells were routinely cultured. si-NC, si-SNRPA#1, si-SNRPA#2 were transfected into HepG2 and Hep3B cells and recorded as si-NC, si-SNRPA#1 and si-SNRPA#2 group. SNRPA-vectors and SNRPA-oe vectors were transfected into LO2 cells and recorded as SNRP-vector and SNRPA-oe group. qPCR was used to detect the expression of SNRPA mRNA in normal hepatocytes and HCC cells, as well as HepG2 and Hep3B cells transfected with each group. MTT, Transwell and WB assays were used to respectively investigate the changes in the proliferation, migration and invasion abilities as well as the expression of EMT-related proteins in the transfected HepG2 and Hep3B cells in each group. Results: Database analysis showed that SNRPA mRNA was highly expressed in the majority of tumors (all P<0.001) and correlated with their pathological stages (P<0.05 or P<0.01). SNRPA was highly expressed in both HCC tissues and HCC cells (P<0.05 or P<0.01) and was correlated with the prognosis of HCC patients (P<0.01). Knockdown of SNRPA expression significantly inhibited the proliferation of HepG2 and Hep3B cells (P<0.05 or P<0.01) while overexpression of SNRPA promoted the proliferation of LO2 cells (P<0.01). Knockdown of SNRPA expression significantly inhibited the migration and invasion abilities of HepG2 and Hep3B cells (both P<0.01) and promoted a marked up-regulation of the expression of E-cadherin (P<0.01) and suppressed the expression of N-cadherin and vimentin (P<0.01). Conclusion: The expression of SNRPA was significantly elevated in HCC tissues and cells, and it may promote the proliferation,migration and invasion of HepG2 and Hep3B cells by regulating the epithelial-mesenchymal transition (EMT) process.
Objective: To investigate the expression of SNRPA in hepatocellular carcinoma (HCC) and cells and the role and mechanism of small nuclear ribonucleoprotein polypeptide A (SNRPA) in regulating the malignant biological behaviors of HCC HepG2 and Hep3B cells. Methods: The database was used to analyze the expression of SNRPA in pan-cancer tissues and its correlation with the pathological stage and the prognosis of HCC patients. HepG2 and Hep3B cells were routinely cultured. si-NC, si-SNRPA#1, si-SNRPA#2 were transfected into HepG2 and Hep3B cells and recorded as si-NC, si-SNRPA#1 and si-SNRPA#2 group. SNRPA-vectors and SNRPA-oe vectors were transfected into LO2 cells and recorded as SNRP-vector and SNRPA-oe group. qPCR was used to detect the expression of SNRPA mRNA in normal hepatocytes and HCC cells, as well as HepG2 and Hep3B cells transfected with each group. MTT, Transwell and WB assays were used to respectively investigate the changes in the proliferation, migration and invasion abilities as well as the expression of EMT-related proteins in the transfected HepG2 and Hep3B cells in each group. Results: Database analysis showed that SNRPA mRNA was highly expressed in the majority of tumors (all P<0.001) and correlated with their pathological stages (P<0.05 or P<0.01). SNRPA was highly expressed in both HCC tissues and HCC cells (P<0.05 or P<0.01) and was correlated with the prognosis of HCC patients (P<0.01). Knockdown of SNRPA expression significantly inhibited the proliferation of HepG2 and Hep3B cells (P<0.05 or P<0.01) while overexpression of SNRPA promoted the proliferation of LO2 cells (P<0.01). Knockdown of SNRPA expression significantly inhibited the migration and invasion abilities of HepG2 and Hep3B cells (both P<0.01) and promoted a marked up-regulation of the expression of E-cadherin (P<0.01) and suppressed the expression of N-cadherin and vimentin (P<0.01). Conclusion: The expression of SNRPA was significantly elevated in HCC tissues and cells, and it may promote the proliferation,migration and invasion of HepG2 and Hep3B cells by regulating the epithelial-mesenchymal transition (EMT) process.
CAI Jingjing
,
LIU Xin
,
LI Zhuoying
,
HAN Tingting
,
GUO Yinjin
,
MA Luyao
,
WANG Xiaoxiong
,
LI Hongsheng
,
LI Quan
,
DU Yaqian
,
LAN Yunyi
,
SHEN Shaocong
,
YANG Ruijiao
,
WU Shunxian
,
LIU Junxi
,
ZHOU Yong
2023, 30(12):1082-1087.
DOI: 10.3872/j.issn.1007-385X.2023.12.007
Abstract:
Objective: To evaluate the HRD (homologous recombination deficiency) status of ovarian cancer patients in the Yunnan region using a HRD detection system developed on polymorphic loci specific to the Chinese population. Methods: A total of 248 ovarian cancer patients admitted to the Yunnan Tumor Hospital between January 2021 and May 2023 were included in this study. The HRD status was evaluated using either the Genomic Scar Score (GSS), which is primarily based on copy number length, type, location,and genomic breakpoints, or the HRD score (a combination of three genomic instability events: allelic loss of heterozygosity (LOH),telomeric allelic imbalance (TAI), and large-scale state transitions (LST)). HRD was defined as positive when the tissue sample had a GSS≥50 or HRD≥42 score, or when harmful BRCA1/2 gene mutation was detected. Results: The study showed that approximately 70.97% of the 248 ovarian cancer patients had a positive HRD status, with a BRCA1/2 gene mutation rate of 30.65%. Stage Ⅲ to Ⅵ stage patients and patients with high-grade serous adenocarcinoma had a higher HRD positivity rate (both P<0.01), and patients with higher HRD scores had a higher frequency of co-occurring other gene mutations (P<0.05). HRD status was associated with pathlogical type, clinical stage and other gene mutations in ovarian cancar (all P<0.01). Conclusion: Ovarian cancer patients in the Yunnan region have a high HRD positivity rate, suggesting that a significant proportion of ovarian cancer patients in this region may benefit from treatment with poly (ADP-ribose) polymerase (PARP) inhibitors.
Objective: To evaluate the HRD (homologous recombination deficiency) status of ovarian cancer patients in the Yunnan region using a HRD detection system developed on polymorphic loci specific to the Chinese population. Methods: A total of 248 ovarian cancer patients admitted to the Yunnan Tumor Hospital between January 2021 and May 2023 were included in this study. The HRD status was evaluated using either the Genomic Scar Score (GSS), which is primarily based on copy number length, type, location,and genomic breakpoints, or the HRD score (a combination of three genomic instability events: allelic loss of heterozygosity (LOH),telomeric allelic imbalance (TAI), and large-scale state transitions (LST)). HRD was defined as positive when the tissue sample had a GSS≥50 or HRD≥42 score, or when harmful BRCA1/2 gene mutation was detected. Results: The study showed that approximately 70.97% of the 248 ovarian cancer patients had a positive HRD status, with a BRCA1/2 gene mutation rate of 30.65%. Stage Ⅲ to Ⅵ stage patients and patients with high-grade serous adenocarcinoma had a higher HRD positivity rate (both P<0.01), and patients with higher HRD scores had a higher frequency of co-occurring other gene mutations (P<0.05). HRD status was associated with pathlogical type, clinical stage and other gene mutations in ovarian cancar (all P<0.01). Conclusion: Ovarian cancer patients in the Yunnan region have a high HRD positivity rate, suggesting that a significant proportion of ovarian cancer patients in this region may benefit from treatment with poly (ADP-ribose) polymerase (PARP) inhibitors.
SHABAHAITI·Wusiman
,
YI Na
,
LIU Zhiqin
,
LU Wanyao
,
ZHONG Xuanyu
,
ZIERDIE·Nuhejieti
,
HOU Qiulian
,
LIU Ling
2023, 30(12):1088-1098.
DOI: 10.3872/j.issn.1007-385X.2023.12.008
Abstract:
Objective: To explore the expression of COX17 in pan-cancerous tissues and its relationship with tumor immune cell infiltration and the prognosis of patients. Methods: The expressions of COX17 in human normal tissues and pan-cancerous tissues and its relationship with the prognosis of patients, the mutation of COX17 gene, the correlation between the expression level of COX17 and tumor immune microenvironment, the correlation between the expression level of COX17 in invasive breast cancer and the clinicopathological characteristics of patients, the genetic mutation and methylation of COX17 gene in breast cancer cells were analyzed, using a variety of public cancer database data. The functional enrichment analysis of the differentially co-expressed genes of COX17 in breast cancer, the construction of the protein interaction network of COX17 and the functional analysis were carried out.Finally, the expression of COX17 protein in breast cancer tissues of Chinese nationals was detected by immunohistochemistry to verify database analysis results. Results: COX17 mRNA is widely distributed in the whole body and highly expressed in most cancer tissues.COX17 protein is highly expressed in breast cancer and other cancer tissues. The expression level of COX17 mRNA significantly affects the prognosis of patients with breast cancer and other cancers. COX17 gene has a high mutation frequency in a variety of cancer tissues, and its main mutation types are missense mutation, amplification and deep deletion. The expression level of COX17 mRNA was correlated with tumor purity and immune cell infiltration in a variety of tumors. The expression level of COX17 was correlated with the clinical stage, the pathological type, lymph node metastasis, the gender and age of patients. Immunohistochemical detection results confirmed that COX17 protein was also highly expressed in the breast cancer tissues of Chinese nationals. The genetic mutation and modification characteristics of COX17 gene in breast cancer were truncation mutation and promoter hypermethylation, respectively,COX17 protein is related to the expressions of ATOX1 and other proteins and forms a complex interaction network. The differentially expressed genes of COX17 in breast cancer mainly involve biological processes such as oxidoreductase activity, protein translation,oxidative phosphorylation and TNF signaling pathway. Conclusion: COX17 is highly expressed in most pan cancers and is related to the immune cell infiltration of a variety of tumors and the prognosis of patients. COX17 is a potential target for clinical treatment of breast cancer.
Objective: To explore the expression of COX17 in pan-cancerous tissues and its relationship with tumor immune cell infiltration and the prognosis of patients. Methods: The expressions of COX17 in human normal tissues and pan-cancerous tissues and its relationship with the prognosis of patients, the mutation of COX17 gene, the correlation between the expression level of COX17 and tumor immune microenvironment, the correlation between the expression level of COX17 in invasive breast cancer and the clinicopathological characteristics of patients, the genetic mutation and methylation of COX17 gene in breast cancer cells were analyzed, using a variety of public cancer database data. The functional enrichment analysis of the differentially co-expressed genes of COX17 in breast cancer, the construction of the protein interaction network of COX17 and the functional analysis were carried out.Finally, the expression of COX17 protein in breast cancer tissues of Chinese nationals was detected by immunohistochemistry to verify database analysis results. Results: COX17 mRNA is widely distributed in the whole body and highly expressed in most cancer tissues.COX17 protein is highly expressed in breast cancer and other cancer tissues. The expression level of COX17 mRNA significantly affects the prognosis of patients with breast cancer and other cancers. COX17 gene has a high mutation frequency in a variety of cancer tissues, and its main mutation types are missense mutation, amplification and deep deletion. The expression level of COX17 mRNA was correlated with tumor purity and immune cell infiltration in a variety of tumors. The expression level of COX17 was correlated with the clinical stage, the pathological type, lymph node metastasis, the gender and age of patients. Immunohistochemical detection results confirmed that COX17 protein was also highly expressed in the breast cancer tissues of Chinese nationals. The genetic mutation and modification characteristics of COX17 gene in breast cancer were truncation mutation and promoter hypermethylation, respectively,COX17 protein is related to the expressions of ATOX1 and other proteins and forms a complex interaction network. The differentially expressed genes of COX17 in breast cancer mainly involve biological processes such as oxidoreductase activity, protein translation,oxidative phosphorylation and TNF signaling pathway. Conclusion: COX17 is highly expressed in most pan cancers and is related to the immune cell infiltration of a variety of tumors and the prognosis of patients. COX17 is a potential target for clinical treatment of breast cancer.
XU Heng
,
ZENG Yonglei
,
HAO Wanrong
,
DING Yanqi
,
XIA Kechun
,
ZHOU Xianyang
,
MA Li
,
WU Yong
,
LENG Yuling
2023, 30(12):1099-1104.
DOI: 10.3872/j.issn.1007-385X.2023.12.009
Abstract:
Objective: To analyze the improvement effects of Yiqi Huoxue decoction on cancer pain and cancer-related fatigue (CRF) in patients with malignant tumors. Methods: 82 patients with malignant tumors (qi and blood deficiency syndrome) who were admitted into the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine and diagnosed with cancer-related fatigue (CRF) between January 2020 and December 2022 were selected and divided into the control group and the observation group by the remainder grouping method of the random number table, with 41 cases in each group. Patients in the control group received conventional symptomatic treatments such as pain relief, vomit stopping and phlegm reduction as well as health and psychological guidance while patients in the observation group was given the Yiqi Huoxue decoction treatment in addition to the intervention administered to the control group. Before and after 4 weeks of treatment (1 course of treatment), the clinical TCM efficacy of the two groups was evaluated by the changes of TCM syndromes scores.The clinical efficacy of CRF was assessed by Revised Piper Fatigue Scale (RPFS). The differences in cancer pain were compared by Numerical Rating Scale (NRS). Peripheral blood fibrinogen (FIB) and D-dimer (D-D) were detected to assess the differences in coagulation function,and the safety of Yiqi Huoxue decoction treatment was assessed by patients’ liver and kidney function indexes. Results: Before treatment,the differences between the TCM syndromes scores, RPFS scores, NRS score, peripheral blood FIB and D-D of the two groups were not statistically significant (all P>0.05). After 4 weeks of treatment, the scores of syndromes such as fatigue and tiredness, pale or sallow complexion, spontaneous sweating, insomnia and forgetfulness and hand and foot numbness well as total scores of both groups decreased compared with those before treatment (all P<0.05), and all the scores of the observation group were lower than those of the control group (all P<0.05), and the clinical TCM efficacy of the observation group was significantly higher than that of the control group (P<0.05). After 4 weeks of treatment the dimension scores and total scores of RPFS of the two groups were reduced compared to those before treatment (all P<0.05). The dimension scores of behaviors, emotion and feeling and total score of RPFS of the observation group were lower than those of the control group (all P<0.05) while the clinical efficacy of CRF was significantly higher than that of the control group (P<0.05). After 4 weeks of treatment, NRS score and peripheral blood FIB and D-D of both groups were reduced compared with those before treatment (all P<0.05), and the scores of the observation group were lower than those of the control group (all P<0.05). No obvious abnormal indicators of liver function and kidney function occurred in the two groups during treatment, suggesting that Yiqi Huoxue decoction was safe.Conclusion: Yiqi Huoxue decoction can correct the syndrome of qi and blood deficiency, improve the body’ s coagulation function, and promote the relief of CRF and cancer pain in patients with malignant tumors. Therefore, it has high clinical application value.
Objective: To analyze the improvement effects of Yiqi Huoxue decoction on cancer pain and cancer-related fatigue (CRF) in patients with malignant tumors. Methods: 82 patients with malignant tumors (qi and blood deficiency syndrome) who were admitted into the Second Affiliated Hospital of Anhui University of Traditional Chinese Medicine and diagnosed with cancer-related fatigue (CRF) between January 2020 and December 2022 were selected and divided into the control group and the observation group by the remainder grouping method of the random number table, with 41 cases in each group. Patients in the control group received conventional symptomatic treatments such as pain relief, vomit stopping and phlegm reduction as well as health and psychological guidance while patients in the observation group was given the Yiqi Huoxue decoction treatment in addition to the intervention administered to the control group. Before and after 4 weeks of treatment (1 course of treatment), the clinical TCM efficacy of the two groups was evaluated by the changes of TCM syndromes scores.The clinical efficacy of CRF was assessed by Revised Piper Fatigue Scale (RPFS). The differences in cancer pain were compared by Numerical Rating Scale (NRS). Peripheral blood fibrinogen (FIB) and D-dimer (D-D) were detected to assess the differences in coagulation function,and the safety of Yiqi Huoxue decoction treatment was assessed by patients’ liver and kidney function indexes. Results: Before treatment,the differences between the TCM syndromes scores, RPFS scores, NRS score, peripheral blood FIB and D-D of the two groups were not statistically significant (all P>0.05). After 4 weeks of treatment, the scores of syndromes such as fatigue and tiredness, pale or sallow complexion, spontaneous sweating, insomnia and forgetfulness and hand and foot numbness well as total scores of both groups decreased compared with those before treatment (all P<0.05), and all the scores of the observation group were lower than those of the control group (all P<0.05), and the clinical TCM efficacy of the observation group was significantly higher than that of the control group (P<0.05). After 4 weeks of treatment the dimension scores and total scores of RPFS of the two groups were reduced compared to those before treatment (all P<0.05). The dimension scores of behaviors, emotion and feeling and total score of RPFS of the observation group were lower than those of the control group (all P<0.05) while the clinical efficacy of CRF was significantly higher than that of the control group (P<0.05). After 4 weeks of treatment, NRS score and peripheral blood FIB and D-D of both groups were reduced compared with those before treatment (all P<0.05), and the scores of the observation group were lower than those of the control group (all P<0.05). No obvious abnormal indicators of liver function and kidney function occurred in the two groups during treatment, suggesting that Yiqi Huoxue decoction was safe.Conclusion: Yiqi Huoxue decoction can correct the syndrome of qi and blood deficiency, improve the body’ s coagulation function, and promote the relief of CRF and cancer pain in patients with malignant tumors. Therefore, it has high clinical application value.
2023, 30(12):1105-1109.
DOI: 10.3872/j.issn.1007-385X.2023.12.010
Abstract:
肾癌是泌尿系统最常见的肿瘤之一，早期临床表现不典型，经手术治疗后仍有部分发生复发和转移，病死率高。因此，肾癌的早期诊断和晚期治疗成为亟待解决的两大问题。以YAP/TAZ为核心的Hippo 通路在肾癌的发生发展中发挥着重要作用，YAP/TAZ通过直接调控肾癌细胞的转录活性、内源性竞争RNA（ceRNA）机制、促进血管形成、增强肾细胞铁死亡敏感性以及作为肾癌细胞中其他信号通路的转导枢纽等多种机制，促进肾癌细胞的侵袭、转移和耐药；除此之外，YAP/TAZ在多种罕见的肾癌组织学亚型中起到指导分型和预测预后的作用。对于YAP/TAZ在肾癌中的作用及其机制的认识可为临床肾癌的早期诊断和晚期治疗提供理论参考依据。
肾癌是泌尿系统最常见的肿瘤之一，早期临床表现不典型，经手术治疗后仍有部分发生复发和转移，病死率高。因此，肾癌的早期诊断和晚期治疗成为亟待解决的两大问题。以YAP/TAZ为核心的Hippo 通路在肾癌的发生发展中发挥着重要作用，YAP/TAZ通过直接调控肾癌细胞的转录活性、内源性竞争RNA（ceRNA）机制、促进血管形成、增强肾细胞铁死亡敏感性以及作为肾癌细胞中其他信号通路的转导枢纽等多种机制，促进肾癌细胞的侵袭、转移和耐药；除此之外，YAP/TAZ在多种罕见的肾癌组织学亚型中起到指导分型和预测预后的作用。对于YAP/TAZ在肾癌中的作用及其机制的认识可为临床肾癌的早期诊断和晚期治疗提供理论参考依据。
2023, 30(12):1110-1115.
DOI: 10.3872/j.issn.1007-385X.2023.12.011
Abstract:
局晚期非小细胞肺癌（NSCLC）患者治疗多采用放化疗联合的综合治疗模式，免疫检查点抑制剂（ICI）的加入显著改善了其疗效。放疗可通过诱导肿瘤细胞免疫原性死亡、刺激肿瘤细胞自身抗原释放、增加抗原提呈等机制，与免疫治疗产生协同抗肿瘤作用。基于放疗和免疫治疗的协同作用机制，以及PACIFIC 研究的成功，一系列关于放疗联合ICI 的临床研究在NSCLC中相继展开，研究组合形式各异，对于最佳组合方案仍无定论。对于放疗与免疫治疗联合的作用机制、介入时机和联合模式相关的最新临床研究进展的了解具有重要的临床意义。
局晚期非小细胞肺癌（NSCLC）患者治疗多采用放化疗联合的综合治疗模式，免疫检查点抑制剂（ICI）的加入显著改善了其疗效。放疗可通过诱导肿瘤细胞免疫原性死亡、刺激肿瘤细胞自身抗原释放、增加抗原提呈等机制，与免疫治疗产生协同抗肿瘤作用。基于放疗和免疫治疗的协同作用机制，以及PACIFIC 研究的成功，一系列关于放疗联合ICI 的临床研究在NSCLC中相继展开，研究组合形式各异，对于最佳组合方案仍无定论。对于放疗与免疫治疗联合的作用机制、介入时机和联合模式相关的最新临床研究进展的了解具有重要的临床意义。
2023, 30(12):1116-1122.
DOI: 10.3872/j.issn.1007-385X.2023.12.012
Abstract:
复杂的肿瘤微环境（TME）是导致胃癌高度异质性的主要原因之一。外泌体是多囊泡体和质膜融合后释放到体液中形成的纳米级生物囊泡，是TME中的重要组成部分。外泌体携带的生物分子通过促进细胞间的信号交流，在一定程度上参与调控癌症的发生和转移。环状RNA（circRNA）是稳定存在于外泌体中的非编码RNA，其作为miRNA 分子海绵，抑制miRNA 与mRNA 的结合，进而调节下游靶基因mRNA 的表达，并由此形成circRNA-miRNA-mRNA 网络。外泌体中circRNA-miRNA-mRNA网络通过参与调节胃癌的增殖、迁移和侵袭，诱导胃癌细胞上皮间质转化（EMT），介导胃癌血管生成，调节胃癌转移，调控胃癌的化疗耐药以及放射敏感性，在胃癌的发生发展中发挥重要作用。此外，以外泌体中circRNA 为靶点或者靶向circRNA-miRNA-mRNA网络可能为胃癌的治疗提供新的治疗选择。
复杂的肿瘤微环境（TME）是导致胃癌高度异质性的主要原因之一。外泌体是多囊泡体和质膜融合后释放到体液中形成的纳米级生物囊泡，是TME中的重要组成部分。外泌体携带的生物分子通过促进细胞间的信号交流，在一定程度上参与调控癌症的发生和转移。环状RNA（circRNA）是稳定存在于外泌体中的非编码RNA，其作为miRNA 分子海绵，抑制miRNA 与mRNA 的结合，进而调节下游靶基因mRNA 的表达，并由此形成circRNA-miRNA-mRNA 网络。外泌体中circRNA-miRNA-mRNA网络通过参与调节胃癌的增殖、迁移和侵袭，诱导胃癌细胞上皮间质转化（EMT），介导胃癌血管生成，调节胃癌转移，调控胃癌的化疗耐药以及放射敏感性，在胃癌的发生发展中发挥重要作用。此外，以外泌体中circRNA 为靶点或者靶向circRNA-miRNA-mRNA网络可能为胃癌的治疗提供新的治疗选择。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.