MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3

Liu,Yanqi; Sun,Yanhong; Zhao,Aizhen

doi:10.3892/or.2017.5488

MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3

Authors:
- Yanqi Liu
- Yanhong Sun
- Aizhen Zhao
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Affiliations: Department of Gastroenterology, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China, Department of Physiology, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China, Department of Ultrasound, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China
Published online on: March 2, 2017 https://doi.org/10.3892/or.2017.5488
Pages: 2441-2448

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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.

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