title: 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 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.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Guangyan
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China.
authors.forename: Shiyu
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Zhenjuan
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Xue
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D014162:Transfection; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D042582:Vascular Endothelial Growth Factor C; D008156:Luciferases; D002945:Cisplatin