MiR-129-5p Restrains Apatinib Resistance in Human Gastric Cancer Cells Via Downregulating HOXC10

Background: Repeated administration of apatinib has resulted in serious drug resistance in gastric cancer (GC). Previous studies showed that miR-129-5p had a low expression in GC, and homeobox gene C10 (HOXC10), a carcinogenic gene, was highly expressed in GC, while the molecular mechanism of miR-129-5p involved in apatinib resistance in GC cells is still unclear. Materials and Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-129-5p and HOXC10 in GC tissues or cell lines. The expression levels of associated proteins were detected by Western blot. Cell counting kit-8 (CCK-8), the 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), and flow cytometry assays were conducted to detect cell viability, proliferation, and apoptosis of MGC-803/AP and AGS/AP cells in vitro. The dual-luciferase reporter assay was used to verify the targeted relationship between miR-129-5p and HOXC10. The xenograft model was established to examine the effect of miR-129-5p in vivo, and the HOXC10 protein expression in tumor xenograft was assessed by immunohistochemistry. Results:MiR-129-5p had a low expression in GC tissues and apatinib-resistant cell lines, while HOXC10 was highly expressed. Meanwhile, overexpression of miR-129-5p and knockdown of HOXC10 could enhance the chemosensitivity of MGC-803/AP and AGS/AP cells. Dual-luciferase reporter assay confirmed miR-129-5p targeted HOXC10 and downregulated its expression level. MiR-129-5p inhibited proliferation and promoted apoptosis of MGC-803/AP and AGS/AP cells by downregulating HOXC10. The experiment in vivo also confirmed that miR-129-5p reduced apatinib resistance in GC cells by targetedly inhibiting HOXC10. HOXC10 was upregulated in GC tumor xenograft tissues. Conclusion:miR-129-5p restrains apatinib-resistant of GC cells by regulating HOXC10.