MicroRNA-101 induces apoptosis in cisplatin-resistant gastric cancer cells by targeting VEGF-C.

Deregulation of microRNAs (miRNAs) is known to be associated with drug resistance in human cancers. However, the precise role of miR‑101 in the cisplatin (DPP) resistance of human gastric cancer cells has not been elucidated, yet. The present study revealed that miR‑101 was markedly downregulated in gastric cancer cell lines compared to that in the normal gastric mucosa epithelial cell line GES1. Furthermore, a significant decrease in miR‑101 levels, accompanied with an increased expression of vascular endothelial growth factor (VEGF)‑C in DDP‑resistant SGC7901 gastric cancer cells (SGC7901/DDP) compared with those in native SGC7901 cells was observed. In addition, forced overexpression of miR‑101 significantly inhibited cell proliferation, while enhancing cisplatin‑induced apoptosis of SGC7901/DDP cells. A luciferase reporter assay confirmed that VEGF‑C was a direct target of miR‑101 in SGC7901/DDP cells. Forced overexpression of miR‑101 in SGC7901/DDP cells reduced the expression of VEGF‑C, while knockdown of miR‑101 expression significantly enhanced VEGF‑C expression in SGC7901/DDP cells. Finally, overexpression of VEGF‑C inhibited DDP‑induced apoptosis in SGC7901 cells. In conclusion, the results of the present study suggested that miR‑101 inhibited the proliferation and promoted DDP‑induced apoptosis of DDP‑resistant gastric cancer cells, at least in part via targeting VEGF-C.