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Archive > Volume 31 Issue 4 > 2024,31(4):342-350. DOI:10.3872/j.issn.1007-385X.2024.04.004 Prev Next
Basic Research
NCOR2 promotes the migration and invasion of esophageal squamous cell carcinoma KYSE450 cells by regulating the PI3K/AKT signaling pathway
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Abstract:
Objective: To explore the role of nuclear receptor corepressor 2 (NCOR2) gene in the carcinogenesis and progression of esophageal squamous cell carcinoma (ESCC) and investigate its underlying molecular regulatory mechanism. Methods: Tumor tissue specimens, adjacent tissue specimens and clinical data of 155 ESCC patients diagnosed in Shanxi Tumor Hospital between May 2017 and July 2018 were collected. Transcriptome and clinicopathological data of patients were used for survival prognosis analysis and clinical association analysis. qPCR assay was conducted to detect the expression levels of NCOR2 gene in six ESCC cell lines (TE-1,TE-5, TE-9, KYSE150, KYSE180 and KYSE450). KYSE450 cells with highly-expressed NCOR2 gene were selected for siRNA knockdown experiment and construction of knockdown NCOR2 cell model. CCK-8 cell viability assay, colony formation assay, wound healing assay and Transwell assay were performed to explore the effect of NCOR2 knockdown on proliferation vitality, clone formation, invasion and migration abilities of KYSE450 cells. Transcriptome sequencing analysis was conducted on NCOR2 knockdown KYSE450 cells to identify differentially expressed genes. GO (Gene Ontology, GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes, KEGG) analysis were performed to characterize the signal regulation network that might be affected by NCOR2.Results: The expression of NCOR2 in ESCC tumor tissues was significantly higher than that in the adjacent tissues (P<0.01). Poor prognosis were associated with higher expression of NCOR2 in ESCC patients (P<0.05). The knocking-down of NCOR2 significantly reduced wound healing rate and cell migration and invasion abilities of KYSE450 cells (all P<0.01). However, cell proliferation and colony formation abilities were not significantly affected (all P>0.05). After NCOR2 knockdown in KYSE450 cells, transcriptome sequencing analysis revealed that 54 genes were significantly up-regulated and 127 genes were significantly down-regulated. KEGG analysis results showed that the significantly differentially expressed genes were enriched in PI3K/AKT signaling pathway (P<0.01). In the transcriptome data of the clinical samples of the 155 ESCC patients, the expression levels of the 4 genes PIK3R3, IL4R, COL1A1 and EFNA1 of the PI3K/AKT pathway were significantly correlated with NCOR2 (all P<0.01), which was consistent with the transcriptome sequencing analysis results. Conclusion: NCOR2 can promote the invasion and migration of KYSE450 cells via the PI3K/AKT signaling pathway, thus affecting ESCC carcinogenesis and progression.
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