title: MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3.
abstract: Emerging evidence has shown that microRNAs (miRNAs) play critical roles in tumor development and progression. miR-134 has been found to act as a tumor-suppressor in numerous types of cancers. However, little is known concerning the potential role of miR-134 in gastric carcinogenesis. In the present study, we found that miR-134 was highly downregulated in gastric cancer tissues and cell lines when compared with levels in their adjacent non-tumor tissues and the normal human gastric epithelial cell line GES-1. Additionally, overexpression of miR-134 was accompanied by reduced cell proliferation in vitro and decreased tumor size in vivo. Further investigation by luciferase reporter assay indicated that Golgi phosphoprotein 3 (GOLPH3), a potent oncogene, was a direct target of miR-134. The activity of a luciferase reporter carrying the miR-134 binding site in the 3'-untranslated region (3'-UTR) of GOLPH3 was repressed by overexpression of miR-134, while a mutation in the 3'-UTR of GOLPH3 abrogated this effect, indicating that GOLPH3 is a target gene of miR-134. Overexpression of GOLPH3 blocked the antiproliferative effect of pre-miR-134 in gastric carcinoma cells. Furthermore, overexpression of miR-134 was associated with decreased phosphorylation of AKT, mTOR and S6K. Taken together, these data suggest that miR-134 regulates gastric cancer cell proliferation, at least potentially, through downregulation of the GOLPH3 gene, implicating a candidate tumor-suppressor miRNA in the pathogenesis of gastric cancer.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Ultrasound, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
chemical_list: D020413:3' Untranslated Regions; C429024:GOLPH3 protein, human; C569273:MIRN134 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs