Effect of cyclic RNA-102231 on cisplatin resistance in HT-29 colon cancer cells and its mechanism / 中华普通外科杂志

ABSTRACT

Objective:To investigate the effect of circRNA-102231 on the sensitivity of colon cancer HT-29 cells to cisplatin and its mechanism.Methods:The expression of circRNA-102231 and ABCB1 were detected by Western blot and RT-qPCR in cisplatin-resistant HT-29/DDP cell lines. Overexpress or knockdown circRNA-102231 in HT-29 cells were respectively followed by treatment with cisplatin, CCK-8 method was used to detect cell viability, Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of circ-102231 and ABCB1; The circRNA-102231 combined microRNA was predicted by the database and verified with RT-qPCR; Activation or inhibition of ERK and overexpression of miR-145, Western blot and RT-qPCR were used to detect the protein and mRNA levels of ABCB1, and the luciferase reporter assay was used to detect the ABCB1 promoter activity.Results:Compared with HT-29 cells, the expression levels of circRNA-102231 and ABCB1 were significantly up-regulated in HT-29/DDP cells(all P<0.05). Overexpression of circRNA-102231 up-regulated the expression of ABCB1 and decreased the sensitivity of cells to cisplatin( P<0.05). Knockdown of circRNA-102231 down-regulated the expression of ABCB1, hence increased the sensitivity to cisplatin( P<0.05); circRNA-102231 can recruit miR-145 and promote its expression; miR-145 induce ERK phosphorylation, activation or inhibition of ERK activity can promote or up regulate the expression level and promote activity of ABCB1( P<0.05). Conclusion:circRNA-102231 may increase the resistance of HT-29 cells to cisplatin by promoting the up-regulation of ABCB1 through miRNA-145/ERK pathway.