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2025,32(2):127-139, DOI: 10.3872/j.issn.1007-385X.2025.02.001
Abstract:
[Abstract] Hematologic malignancies are a severe threat to human health. CAR-T cell therapy, as a highly effective treatment for hematologic malignancies, has become one of the fastest developing cancer immunotherapies in recent years. To obtain highly effective and low-toxicity CAR-T cells, through continuous development and exploration, CAR-T cell therapy has achieved a series of significant breakthroughs in treating hematologic malignancies, including humanized CAR-T cell technology, dual-target and multitarget CAR-T cell technology, universal CAR-T cell technology, and CAR-T cell combination strategy technology. Humanized CAR-T cell technology reduces immunogenicity through humanized modification. Dual-target and multi-target CAR-T cell technology recognizes two or more tumor antigens, minimizes antigen escape and enhance efficacy. Universal CAR-T cell technology solves problems such as high cost and accessibility issues. The CAR-T cell combination strategy technology effectively deals with CAR-T recurrence and enhances efficacy and safety by combining different treatment methods. Although CAR-T cell therapy has achieved significant breakthroughs in the treatment of hematologic malignancies, it still faces challenges such as drug resistance, antigen escape, cytotoxicity, and posttreatment recurrence. This review presents the significant breakthroughs, existing problems, and solutions for CAR-T cell precise therapy for hematological malignancies.
[Abstract] Hematologic malignancies are a severe threat to human health. CAR-T cell therapy, as a highly effective treatment for hematologic malignancies, has become one of the fastest developing cancer immunotherapies in recent years. To obtain highly effective and low-toxicity CAR-T cells, through continuous development and exploration, CAR-T cell therapy has achieved a series of significant breakthroughs in treating hematologic malignancies, including humanized CAR-T cell technology, dual-target and multitarget CAR-T cell technology, universal CAR-T cell technology, and CAR-T cell combination strategy technology. Humanized CAR-T cell technology reduces immunogenicity through humanized modification. Dual-target and multi-target CAR-T cell technology recognizes two or more tumor antigens, minimizes antigen escape and enhance efficacy. Universal CAR-T cell technology solves problems such as high cost and accessibility issues. The CAR-T cell combination strategy technology effectively deals with CAR-T recurrence and enhances efficacy and safety by combining different treatment methods. Although CAR-T cell therapy has achieved significant breakthroughs in the treatment of hematologic malignancies, it still faces challenges such as drug resistance, antigen escape, cytotoxicity, and posttreatment recurrence. This review presents the significant breakthroughs, existing problems, and solutions for CAR-T cell precise therapy for hematological malignancies.
PAN Yingjie, SUN Shan, YANG Hang, TAN Jinsong, CHEN Qiaoling, ZHAO Quanneng, YANG Mi, LIU Kang, SONG Guiqin
2025,32(2):140-150, DOI: 10.3872/j.issn.1007-385X.2025.02.002
Abstract:
[Abstract] Objective: To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins (WTAP) on the cell biological properties of esophageal squamous cell carcinoma (ESCC) cells. Methods: 31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected. The esophageal cancer cells KYSE30, KYSE410, KYSE150, KYSE510, TE-1, and normal human esophageal epithelial cells HET-1A were routinely cultured. Transfection reagents were used to transfect si-NC, si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells. The cells were divided into si-NC, si-WTAP#1 and si-WTAP#2 groups. The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay. CCK-8 assay, clone formation assay, and scratch healing assay, Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation, migration, invasion and apoptosis. WB assay was used to detect the expressions of WTAP, MAP3K9, EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP; immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues, immunoprecipitation of methylated RNA (MeRIP)-qPCR assay to detect the level of MAP3K9 m6 A in ESCC cells, actinomycin D assay to detect the stability of mRNA of MAP3K9, and database data to analyze the expression, target genes, functional enrichment, and interacting RNA of WTAP. Results: WTAP was highly expressed in ESCC tissues and cells (P < 0.05 or P < 0.01 or P < 0.001) and correlated with the degree of differentiation (P < 0.01); the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells (P < 0.01 or P < 0.001); the knockdown of WTAP significantly inhibited the proliferation, migration and invasion of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01 or P < 0.001), and promoted the apoptosis of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01). Knockdown of WTAP resulted in a significant decrease in the m6 A level of MAP3K9 (P < 0.05), and its mRNA expression level and mRNA stability were both significantly reduced (P < 0.05). Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway; the expression levels of MAP3K9, p-ERK, N-cadherin, and MMP9 were significantly reduced (P < 0.05 or P < 0.01), and the expression level of E-cadherin was significantly elevated (P < 0.05 or P < 0.01) in the KYSE150 and KYSE510 cells after knockdown of WTAP. Conclusions: WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation. It promotes the stability of MAP3K9 mRNA through m6 A modification, activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.
[Abstract] Objective: To investigate the effects and molecular mechanisms of Wilms tumor 1-associated proteins (WTAP) on the cell biological properties of esophageal squamous cell carcinoma (ESCC) cells. Methods: 31 pairs of ESCC tissues and their paired paracancerous tissues that were surgically resected at the Second Clinical Medical College of Chuanbei Medical College between September 2019 and April 2021 were collected. The esophageal cancer cells KYSE30, KYSE410, KYSE150, KYSE510, TE-1, and normal human esophageal epithelial cells HET-1A were routinely cultured. Transfection reagents were used to transfect si-NC, si-WTAP#1 and si-WTAP#2 nucleic acids into KYSE150 and KYSE510 cells. The cells were divided into si-NC, si-WTAP#1 and si-WTAP#2 groups. The expressions of WTAP and MAP3K9 mRNA were detected in the cells of each group by qPCR assay. CCK-8 assay, clone formation assay, and scratch healing assay, Transwell assay were employed to detect the effects of knockdown of WTAP expression on ESCC cell proliferation, migration, invasion and apoptosis. WB assay was used to detect the expressions of WTAP, MAP3K9, EMT and MAPK pathway-related proteins in ESCC cells of each group knocked down of WTAP; immunohistochemistry to detect the expression of WTAP proteins in ESCC tissues, immunoprecipitation of methylated RNA (MeRIP)-qPCR assay to detect the level of MAP3K9 m6 A in ESCC cells, actinomycin D assay to detect the stability of mRNA of MAP3K9, and database data to analyze the expression, target genes, functional enrichment, and interacting RNA of WTAP. Results: WTAP was highly expressed in ESCC tissues and cells (P < 0.05 or P < 0.01 or P < 0.001) and correlated with the degree of differentiation (P < 0.01); the expression of WTAP mRNA and its protein were successfully knocked down in KYSE150 and KYSE510 cells (P < 0.01 or P < 0.001); the knockdown of WTAP significantly inhibited the proliferation, migration and invasion of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01 or P < 0.001), and promoted the apoptosis of KYSE150 and KYSE510 cells (P < 0.05 or P < 0.01). Knockdown of WTAP resulted in a significant decrease in the m6 A level of MAP3K9 (P < 0.05), and its mRNA expression level and mRNA stability were both significantly reduced (P < 0.05). Database data analysis showed that WTAP target genes clustered in the MAPK signaling pathway; the expression levels of MAP3K9, p-ERK, N-cadherin, and MMP9 were significantly reduced (P < 0.05 or P < 0.01), and the expression level of E-cadherin was significantly elevated (P < 0.05 or P < 0.01) in the KYSE150 and KYSE510 cells after knockdown of WTAP. Conclusions: WTAP is highly expressed in ESCC tissues and cells and correlates with their differentiation. It promotes the stability of MAP3K9 mRNA through m6 A modification, activates the MAPK pathway and thus promotes the malignant biological behaviors of ESCC cells.
2025,32(2):151-160, DOI: 10.3872/j.issn.1007-385X.2025.02.003
Abstract:
[Abstract] Objective: To investigate the role of SiHa cell-derived exosomal hsa-miR-29c-3p in the angiogenesis of cervical cancer (CC). Methods: Cancer tissue specimens from 45 patients with cervical squamous cell carcinoma (CSCC) and normal cervical tissue specimens from 15 controls were collected from Department of Gynecology, Hengyang Central Hospital from January 2019 to December 2021. CSCC SiHa cells and human umbilical vein endothelial cells （HUVECs）were routinely cultured. miRNA-NC, hsa-miR-29c-3p, si-miRNA-NC, and si-hsa-miR-29c-3p were transfected into SiHa cells with Lipofectamine 2000, grouped as miRNA-NC group, hsa-miR-29c-3p group, si-miRNA-NC group and si-hsa-miR-29c-3p group, respectively. HUVECs were transfected with mimic-NC, miR-29c-3p-mimic, pCMV-NC, and pCMV-ATAD2B (ATPase family protein 2B with AAA domain) using Lipofectamine 2000, grouped as the mimic-NC group, miR-29c-3p-mimic group, pCMV-NC group, pCMV-ATAD2B group, and pCMV-ATAD2B + miR-29c-3p-mimic group. The expression of hsa-miR-29c-3p in CSCC tissues was detected by in situ hybridization (ISH), and CD31-positive blood vessels in CSCC tissues and xenograft tissues were detected by immunohistochemistry (IHC). Exosomes from SiHa and C33a cells were isolated and characterized using transmission electron microscopy (TEM) and western blotting (WB). The uptake of exosomes by HUVECs was examined. The expression of hsa-miR-29c-3p and ATAD2B mRNA in SiHa and C33a cells, as well as in their derived exosomes, was detected using qPCR. Tube-forming assay, Transwell assay, and scratch healing assay were performed to detect the effect of exosomes on the ability of HUVEC migration and tube formation. Dual luciferase reporter gene assay verified the interaction between hsa-miR-29c-3p and ATAD2B. Xenograft experiments examined the effects of SiHa cell-derived exosomes on transplanted tumor growth and angiogenesis in each group. Results: hsa-miR-29c-3p was highly expressed in CSCC tissues and was positively correlated with microvessel density (MVD) (all P < 0.05). Exosomes derived from SiHa and C33a cells exhibited typical exosomal morphology and protein expression patterns. Exosomal hsa-miR-29c-3p from SiHa and C33a cells were efficiently taken up by HUVECs in vitro. The SiHa cell-derived exosomal hsa-miR-29c-3p promoted not only the tube-forming and migration of HUVECs in vitro but also the xenograft growth and angiogenesis in vivo (all P < 0.05). hsa-miR-29c-3p directly targeted ATAD2B and regulated its expression (P < 0.05). Overexpression of ATAD2B reversed the promotive effect of hsa-miR-29c-3p on tube-formation, migration, and scratch-healing in HUVECs (all P < 0.05). Conclusion: SiHa cell-derived exosomal hsa-miR-29c-3p regulates angiogenesis in CSCC tissues by targeting ATAD2B. Exosomal hsa-miR-29c-3p may be a potential diagnostic marker and therapeutic target for CC diagnosis and treatment.
[Abstract] Objective: To investigate the role of SiHa cell-derived exosomal hsa-miR-29c-3p in the angiogenesis of cervical cancer (CC). Methods: Cancer tissue specimens from 45 patients with cervical squamous cell carcinoma (CSCC) and normal cervical tissue specimens from 15 controls were collected from Department of Gynecology, Hengyang Central Hospital from January 2019 to December 2021. CSCC SiHa cells and human umbilical vein endothelial cells （HUVECs）were routinely cultured. miRNA-NC, hsa-miR-29c-3p, si-miRNA-NC, and si-hsa-miR-29c-3p were transfected into SiHa cells with Lipofectamine 2000, grouped as miRNA-NC group, hsa-miR-29c-3p group, si-miRNA-NC group and si-hsa-miR-29c-3p group, respectively. HUVECs were transfected with mimic-NC, miR-29c-3p-mimic, pCMV-NC, and pCMV-ATAD2B (ATPase family protein 2B with AAA domain) using Lipofectamine 2000, grouped as the mimic-NC group, miR-29c-3p-mimic group, pCMV-NC group, pCMV-ATAD2B group, and pCMV-ATAD2B + miR-29c-3p-mimic group. The expression of hsa-miR-29c-3p in CSCC tissues was detected by in situ hybridization (ISH), and CD31-positive blood vessels in CSCC tissues and xenograft tissues were detected by immunohistochemistry (IHC). Exosomes from SiHa and C33a cells were isolated and characterized using transmission electron microscopy (TEM) and western blotting (WB). The uptake of exosomes by HUVECs was examined. The expression of hsa-miR-29c-3p and ATAD2B mRNA in SiHa and C33a cells, as well as in their derived exosomes, was detected using qPCR. Tube-forming assay, Transwell assay, and scratch healing assay were performed to detect the effect of exosomes on the ability of HUVEC migration and tube formation. Dual luciferase reporter gene assay verified the interaction between hsa-miR-29c-3p and ATAD2B. Xenograft experiments examined the effects of SiHa cell-derived exosomes on transplanted tumor growth and angiogenesis in each group. Results: hsa-miR-29c-3p was highly expressed in CSCC tissues and was positively correlated with microvessel density (MVD) (all P < 0.05). Exosomes derived from SiHa and C33a cells exhibited typical exosomal morphology and protein expression patterns. Exosomal hsa-miR-29c-3p from SiHa and C33a cells were efficiently taken up by HUVECs in vitro. The SiHa cell-derived exosomal hsa-miR-29c-3p promoted not only the tube-forming and migration of HUVECs in vitro but also the xenograft growth and angiogenesis in vivo (all P < 0.05). hsa-miR-29c-3p directly targeted ATAD2B and regulated its expression (P < 0.05). Overexpression of ATAD2B reversed the promotive effect of hsa-miR-29c-3p on tube-formation, migration, and scratch-healing in HUVECs (all P < 0.05). Conclusion: SiHa cell-derived exosomal hsa-miR-29c-3p regulates angiogenesis in CSCC tissues by targeting ATAD2B. Exosomal hsa-miR-29c-3p may be a potential diagnostic marker and therapeutic target for CC diagnosis and treatment.
2025,32(2):161-168, DOI: 10.3872/j.issn.1007-385X.2025.02.004
Abstract:
[Abstract] Objective: To explore the mechanism of lncRNA FOXD2-AS1 regulating the expression of LATS1 via EZH2 to affect the proliferation and migration of clear cell renal cell carcinoma (ccRCC) cells. Methods: The GEPIA 2 online tool was used to analyze the expression levels of FOXD2-AS1 in ccRCC tissues from the Cancer Genome Atlas (TCGA) database, and their correlation with patients’ overall survival rates was evaluated. Quantitative PCR (qPCR) was performed to analyze the expressions of FOXD2-AS1 in renal cancer cells and 26 clinically collected ccRCC tissue samples. CCK-8 cell proliferation assay and transwell chamber migration assay were employed to observe the effects of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. qPCR and Western blot analysis were utilized to assess the impact of FOXD2-AS1 knockdown on the expression of LATS1. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between FOXD2-AS1, EZH2, and LATS1. Results: The GEPIA 2 software analysis revealed that FOXD2-AS1 was significantly upregulated in ccRCC tissues (P < 0.01) and patients with high FOXD2-AS1 expression exhibited lower overall survival rates (P < 0.05). The qPCR analysis results showed that FOXD2-AS1 was significantly upregulated in 26 samples of ccRCC tissues compared with adjacent normal kidney tissues (P < 0.01). Compared with immortalized renal tubular epithelial cell line HK-2, the expression of FOXD2-AS1was significantly elevated in three types of renal cancer cell lines (786-O, ACHN and SN12-PM6) (P < 0.01). Knockdown of FOXD2-AS1 expression significantly decreased the proliferation and migration abilities of renal cancer cells (P < 0.05), and markedly increased the mRNA and protein expression levels of LATS1 (all P < 0.01). RIP and ChIP assays confirmed that FOXD2-AS1 can bind and recruit EZH2 to the promoter region of LATS1 to exert its effect. Salvage experiments demonstrated that knocking down LATS1 or overexpressing EZH2 partially reversed the inhibitory effect of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. Conclusion: FOXD2-AS1 is highly expressed in ccRCC, and it negatively regulates the expression of LATS1 by recruiting EZH2 to the promoter region of the LATS1 gene, thereby facilitating the proliferation and migration of renal cancer cells.
[Abstract] Objective: To explore the mechanism of lncRNA FOXD2-AS1 regulating the expression of LATS1 via EZH2 to affect the proliferation and migration of clear cell renal cell carcinoma (ccRCC) cells. Methods: The GEPIA 2 online tool was used to analyze the expression levels of FOXD2-AS1 in ccRCC tissues from the Cancer Genome Atlas (TCGA) database, and their correlation with patients’ overall survival rates was evaluated. Quantitative PCR (qPCR) was performed to analyze the expressions of FOXD2-AS1 in renal cancer cells and 26 clinically collected ccRCC tissue samples. CCK-8 cell proliferation assay and transwell chamber migration assay were employed to observe the effects of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. qPCR and Western blot analysis were utilized to assess the impact of FOXD2-AS1 knockdown on the expression of LATS1. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between FOXD2-AS1, EZH2, and LATS1. Results: The GEPIA 2 software analysis revealed that FOXD2-AS1 was significantly upregulated in ccRCC tissues (P < 0.01) and patients with high FOXD2-AS1 expression exhibited lower overall survival rates (P < 0.05). The qPCR analysis results showed that FOXD2-AS1 was significantly upregulated in 26 samples of ccRCC tissues compared with adjacent normal kidney tissues (P < 0.01). Compared with immortalized renal tubular epithelial cell line HK-2, the expression of FOXD2-AS1was significantly elevated in three types of renal cancer cell lines (786-O, ACHN and SN12-PM6) (P < 0.01). Knockdown of FOXD2-AS1 expression significantly decreased the proliferation and migration abilities of renal cancer cells (P < 0.05), and markedly increased the mRNA and protein expression levels of LATS1 (all P < 0.01). RIP and ChIP assays confirmed that FOXD2-AS1 can bind and recruit EZH2 to the promoter region of LATS1 to exert its effect. Salvage experiments demonstrated that knocking down LATS1 or overexpressing EZH2 partially reversed the inhibitory effect of FOXD2-AS1 knockdown on the proliferation and migration of renal cancer cells. Conclusion: FOXD2-AS1 is highly expressed in ccRCC, and it negatively regulates the expression of LATS1 by recruiting EZH2 to the promoter region of the LATS1 gene, thereby facilitating the proliferation and migration of renal cancer cells.
2025,32(2):169-175, DOI: 10.3872/j.issn.1007-385X.2025.02.005
Abstract:
[Abstract] Objective: To explore the expression of chemokine ligand 1 (CCL1) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration and invasion of human oral tongue squamous cell carcinoma cells (HSC-4). Methods: 28 OSCC tissue samples and clinical characteristic data of patients were collected at the Affiliated Stomatological Hospital of Southwest Medical University between January 2018 and June 2020, as well as 10 normal gingival tissue samples removed during the extraction of impacted teeth. OSCC cells HSC-4 were cultured routinely and divided into the control group (without virus), the NC group (transfected with control lentiviral vector), the shCCL1 group (transfected with knockdown CCL1 lentiviral vector), and the CCL1 group (culture medium containing 60 ng/mL CCL1 recombinant protein). Immunohistochemistry and WB were used to detect the expression of CCL1 in OSCC tissues and cells, and analyze the correlation between its expression level and the clinical features of patients. qPCR, CCK-8 assay, plate cloning assay, cell scratch test, Transwell assay and flow cytometry were used to detect the expression of CCL1 mRNA, the proliferation, migration and invasion abilities and the apoptosis of HSC-4 cells respectively. Results: CCL1 protein was highly expressed in OSCC tissues and HSC-4 cells (all P < 0.01) and its expression was related to the clinical stage of tumors (P < 0.05). The expression of CCL1 in HSC-4 cells was successfully knocked down (P < 0.000 5). Knocking down the expression of CCL1 could inhibit the proliferation (P < 0.05 or P < 0.01), migration and invasion (all P < 0.05) of HSC-4 cells, and promote its apoptosis (all P < 0.05). CCL1 recombinant protein treatment resulted in the opposite effects (P < 0.05, P < 0.01, P < 0.000 1). Conclusion: CCL1 is highly expressed in OSCC and its expression is correlated with the clinical stage of OSCC. CCL1 may take part in regulating the proliferation, migration, invasion and apoptosis of HSC-4 cells.
[Abstract] Objective: To explore the expression of chemokine ligand 1 (CCL1) in oral squamous cell carcinoma (OSCC) and its effect on the proliferation, migration and invasion of human oral tongue squamous cell carcinoma cells (HSC-4). Methods: 28 OSCC tissue samples and clinical characteristic data of patients were collected at the Affiliated Stomatological Hospital of Southwest Medical University between January 2018 and June 2020, as well as 10 normal gingival tissue samples removed during the extraction of impacted teeth. OSCC cells HSC-4 were cultured routinely and divided into the control group (without virus), the NC group (transfected with control lentiviral vector), the shCCL1 group (transfected with knockdown CCL1 lentiviral vector), and the CCL1 group (culture medium containing 60 ng/mL CCL1 recombinant protein). Immunohistochemistry and WB were used to detect the expression of CCL1 in OSCC tissues and cells, and analyze the correlation between its expression level and the clinical features of patients. qPCR, CCK-8 assay, plate cloning assay, cell scratch test, Transwell assay and flow cytometry were used to detect the expression of CCL1 mRNA, the proliferation, migration and invasion abilities and the apoptosis of HSC-4 cells respectively. Results: CCL1 protein was highly expressed in OSCC tissues and HSC-4 cells (all P < 0.01) and its expression was related to the clinical stage of tumors (P < 0.05). The expression of CCL1 in HSC-4 cells was successfully knocked down (P < 0.000 5). Knocking down the expression of CCL1 could inhibit the proliferation (P < 0.05 or P < 0.01), migration and invasion (all P < 0.05) of HSC-4 cells, and promote its apoptosis (all P < 0.05). CCL1 recombinant protein treatment resulted in the opposite effects (P < 0.05, P < 0.01, P < 0.000 1). Conclusion: CCL1 is highly expressed in OSCC and its expression is correlated with the clinical stage of OSCC. CCL1 may take part in regulating the proliferation, migration, invasion and apoptosis of HSC-4 cells.
ZHAO Wei, CUI Wenxuan, HUANG Beixuan, SHANG Xiaoya, WANG Zhenda, DU Yanyan, ZHAO Hongzheng, JIAO Wenjing, MA Ming
2025,32(2):176-188, DOI: 10.3872/j.issn.1007-385X.2025.02.006
Abstract:
[Abstract] Objective: To screen for microRNAs (miRNAs) highly expressed in the serum exosomes (Exo) of esophageal squamous cell carcinoma (ESCC) patients and analyze their relationship with the clinicopathological characteristics of the patients, and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC. Methods: Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected, serving as the control group and the ESCC group respectively. The Gene Expression Omnibus (GEO) database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246. The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve. The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression, and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test. Exosomes in the serum of the subjects were isolated, purified and characterized for verification. The expression of miR-1246 in Exo was detected by qPCR. ESCC KYSE150 and KYSE30 cells were routinely cultured. mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000. Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells, which were respectively denoted as the minics-NC, miR-1246 mimics, inhibitor-NC and miR-1246-inhibitor groups. KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups. The proliferation, migration and invasion abilities of cells in each group were detected by the CCK-8 assay, scratch wound healing assay and Transwell chamber assay respectively. The expressions of Exo markers, epithelial-mesenchymal transition-related proteins, TET family methylcytosine dioxygenase 2 (TET2) and cell adhesion molecule 1 (CADM1) proteins in each group of cells were detected by WB assay. The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay. Results: Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246. The serum Exo extracted from the patients conformed to the typical Exo characteristics. The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects (P < 0.01); the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ (P < 0.01). ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC (P < 0.05), and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag (P < 0.05). The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging (P < 0.01). Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients (P < 0.05). The expression level of serum Exo-miR-1246 was associated with the T-stage, N-stage and clinical stage of ESCC (P < 0.01). Overexpression of miR-1246 could promote the proliferation, migration, invasion, epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells, while inhibition of miR-1246 had the opposite effect. Database data analysis found that TET2 and CADM1 were the target genes of miR-1246. The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions (P < 0.01). Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells. Conclusion: Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC. It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.
[Abstract] Objective: To screen for microRNAs (miRNAs) highly expressed in the serum exosomes (Exo) of esophageal squamous cell carcinoma (ESCC) patients and analyze their relationship with the clinicopathological characteristics of the patients, and to explore the potential of Exo-derived miRNAs as clinical auxiliary diagnostic markers for ESCC. Methods: Serum and relevant clinical data of 50 healthy subjects and 45 newly diagnosed ESCC patients admitted to the Fourth Hospital of Hebei Medical University between December 2021 and June 2023 were collected, serving as the control group and the ESCC group respectively. The Gene Expression Omnibus (GEO) database and qPCR were used to screen and identify the candidate miRNA for increased expression in the serum of ESCC patients-miR-1246. The diagnostic efficacy of serum miR-1246 for ESCC was analyzed by the receiver operating characteristic curve. The relationship between miR-1246 and the clinical feature progression of ESCC patients was analyzed by Logistic regression, and the relationship between miR-1246 and the clinicopathological characteristics of ESCC patients was analyzed by the χ2 test. Exosomes in the serum of the subjects were isolated, purified and characterized for verification. The expression of miR-1246 in Exo was detected by qPCR. ESCC KYSE150 and KYSE30 cells were routinely cultured. mimics-NC and miR-1246 mimics were transfected respectively into KYSE150 cells using Lipofectamine 2000. Inhibitor-NC and miR-1246 inhibitor were transfected into KYSE30 cells, which were respectively denoted as the minics-NC, miR-1246 mimics, inhibitor-NC and miR-1246-inhibitor groups. KYSE150 and KYSE30 cells were treated with Exo derived from KYSE150 cells in the mimics-NC and miR-1246 mimics groups. The proliferation, migration and invasion abilities of cells in each group were detected by the CCK-8 assay, scratch wound healing assay and Transwell chamber assay respectively. The expressions of Exo markers, epithelial-mesenchymal transition-related proteins, TET family methylcytosine dioxygenase 2 (TET2) and cell adhesion molecule 1 (CADM1) proteins in each group of cells were detected by WB assay. The targeting binding relationship between miR-1246 and TET2 and CADM1 was verified by the dual-luciferase reporter gene assay. Results: Bioinformatics screening showed that the miRNA with the most significant differential expression in the serum of ESCC patients was miR-1246. The serum Exo extracted from the patients conformed to the typical Exo characteristics. The expression level of serum Exo-miR-1246 in ESCC patients at stages Ⅰ-Ⅱ was significantly higher than that in healthy subjects (P < 0.01); the level of serum Exo-miR-1246 in ESCC patients at stages Ⅲ-Ⅳ was significantly higher than that in patients at stages Ⅰ-Ⅱ (P < 0.01). ROC curve analysis showed that Exo-miR-1246 in serum had a high value for auxiliary differential diagnosis of ESCC (P < 0.05), and the auxiliary diagnostic efficacy of Exo-miR-1246 for the clinical progression of ESCC patients was higher than that of CEA and SCC-Ag (P < 0.05). The combined detection of the three could further improve the efficacy of auxiliary diagnosis of patient staging (P < 0.01). Exo-miR-1246 might be an independent risk factor for the clinical progression of ESCC patients (P < 0.05). The expression level of serum Exo-miR-1246 was associated with the T-stage, N-stage and clinical stage of ESCC (P < 0.01). Overexpression of miR-1246 could promote the proliferation, migration, invasion, epithelial-mesenchymal transition and inhibit apoptosis of ESCC cells, while inhibition of miR-1246 had the opposite effect. Database data analysis found that TET2 and CADM1 were the target genes of miR-1246. The dual-luciferase reporter gene assay confirmed that miR-1246 could directly bind to TET2 and CADM1 mRNA and inhibit their expressions (P < 0.01). Treatment of KYSE150 and KYSE30 cells with Exo derived from cells overexpressing miR-1246 had the same effect as overexpressing miR-1246 in these cells. Conclusion: Exo-derived miR-1246 has the potential to be a clinical auxiliary diagnostic marker for ESCC. It may affect the occurrence and development of ESCC by regulating the expression levels of TET2 and CADM1.
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2012,19(5):550-555, DOI: 10.3872/j.issn.1007-385X.2012.5.018
Abstract:
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
骨髓增生异常综合征（myelodysplastic syndrome，MDS）的发病机制涉及多阶段、多因素，基因改变与表观遗传修饰可能共同参与了这一过程。DNA甲基化是表观遗传学中一种最为重要的修饰，MDS患者常表现为总体DNA高甲基化。使用DNA甲基转移酶（DNA methyltransferase，DNMT）抑制剂降低总体甲基化水平，在MDS患者中取得了富有成效的临床反应及血液学改善。DNMT抑制剂可分为两类：5-氮杂胞苷(5-azacytidine, 5-Aza-CdR)、地西他滨（5-Aza-2-deoxycytidine, decitabine）等核苷和核苷衍生物类抑制剂，它们可提高MDS患者的临床完全反应率、部分反应率及血液学改善，但缓解率、疗效尚不够令人满意；肼苯哒嗪等非核苷类抑制剂。非核苷类抑制剂与丙戊酸镁联合应用治疗MDS获得成功，为MDS去甲基化治疗药物的研究开启了一种新思路。
2016,23(2):149-160, DOI: 10.3872/j.issn.1007-385X.2016.02.001
Abstract:
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
2018,25(1):23-27, DOI: 10.3872/j.issn.1007-385X.2018.01.004
Abstract:
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
2010,17(1):57-61, DOI: 10.3872/j.issn.1007-385X.2010.1.011
Abstract:
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
Objective: To prepare poly DL lactide poly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase 1 (TIMP 1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP 1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP 1 mRNA in HepG2 cells was examined by semi quantitative RT PCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP 1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP 1 PELA microsphere efficiently induced TIMP 1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP 1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.