miR-29c modulates apatinib resistance in gastric cancer tissues and cell via targeting TNRC18 / 中国肿瘤生物治疗杂志

ABSTRACT

@# Objective: To investigate the mechanism of miR-29c modulating apatinib resistance of gastric cancer tissues and cells MGC-803 via regulating TNRC18. Methods: A total of 39 gastric cancer patients with complete clinical data, who were treated in the Central Hospital of Wuhan from Feb. 2015 to Oct. 2017, were collected for this study. The expression of miR-29c was detected by qRTPCR in gastric cancer tissues and cell lines. The effect of miR-29c over-expression/knockdown on the proliferation, invasion and apoptosis of MGC-803/AP cells in vitro was measured by CCK-8 assay, Transwell and Annexin V-FITC/PI double staining flow cytometry assay. Western blotting was used to detect the regulation of miR-29c on TNRC18. Moreover, the relationship between miR-29c and TNRC18 was examined by dual luciferase reporter gene assay. Results: qRT-PCR revealed that miR-29c was low expressed in gastric cancer cell lines and gastric cancer tissues from patients resistant to apatinib. Moreover, dual luciferase reporter gene assay confirmed that miR-29c directly binds to the 3′UTR of TNRC18 mRNAto suppress its expression in MGC-803/AP cells. Furthermore, miR-29c inhibited the apatinib resistance in gastric cancer MGC-803/AP cells via inhibiting cell proliferation, invasion and promoting cell apoptosis by targeted down-regulating TNRC18. Additionally, in vivo experiment also confirmed that miR-29c modulated apatinib-resistance in gastric cancer cells by targeted inhibiting TNRC18. Conclusion: miR-29c/TNRC18 axis plays a certain role in the resistance of gastric cancer tissues and MGC-803/AP cells to apatinib, and over-expression of miR-29c may reverse the resistance of MGC-803/AP cells to apatinib.