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

ABSTRACT

Deregulation of microRNAs (miRNAs) is known to be associated with drug resistance in human cancers. However, the precise role of miR­101 in the cisplatin (DPP) resistance of human gastric cancer cells has not been elucidated, yet. The present study revealed that miR­101 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 miR­101 levels, accompanied with an increased expression of vascular endothelial growth factor (VEGF)­C in DDP­resistant SGC7901 gastric cancer cells (SGC7901/DDP) compared with those in native SGC7901 cells was observed. In addition, forced overexpression of miR­101 significantly inhibited cell proliferation, while enhancing cisplatin­induced apoptosis of SGC7901/DDP cells. A luciferase reporter assay confirmed that VEGF­C was a direct target of miR­101 in SGC7901/DDP cells. Forced overexpression of miR­101 in SGC7901/DDP cells reduced the expression of VEGF­C, while knockdown of miR­101 expression significantly enhanced VEGF­C expression in SGC7901/DDP cells. Finally, overexpression of VEGF­C inhibited DDP­induced apoptosis in SGC7901 cells. In conclusion, the results of the present study suggested that miR­101 inhibited the proliferation and promoted DDP­induced apoptosis of DDP­resistant gastric cancer cells, at least in part via targeting VEGF-C.