Journal
MOLECULAR MEDICINE REPORTS
Volume 13, Issue 1, Pages 572-578Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2015.4560
Keywords
gastric cancer; microRNA-101; cisplatin; drug resistance; vascular endothelial growth factor
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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 down-regulated 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.
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