Effect of cyclic RNA-102231 on cisplatin resistance in HT-29 colon cancer cells and its mechanism
10.3760/cma.j.cn113855-20200108-00017
- VernacularTitle:环状RNA-102231增加结肠癌HT-29细胞对顺铂耐药性的作用及其机制
- Author:
Peipei WANG
1
;
Jing ZHOU
;
Zheng LI
;
Hai LI
;
Xiao LI
Author Information
1. 河南省驻马店市中心医院临床药学室 463000
- From:
Chinese Journal of General Surgery
2020;35(7):558-562
- CountryChina
- Language:Chinese
-
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.