MicroRNA-134 suppresses cell proliferation in gastric cancer cells via targeting of GOLPH3
| Autor: | Aizhen Zhao, Yanhong Sun, Yanqi Liu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research P70-S6 Kinase 1 Biology medicine.disease_cause 03 medical and health sciences Mice 0302 clinical medicine Stomach Neoplasms Cell Line Tumor medicine Animals Humans 3' Untranslated Regions PI3K/AKT/mTOR pathway Cell Proliferation Oncogene Cell growth Membrane Proteins General Medicine Cell cycle Cell biology Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Carcinogenesis A431 cells Neoplasm Transplantation |
| Zdroj: | Oncology reports. 37(4) |
| ISSN: | 1791-2431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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