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27 April 2016 : Laboratory Research  

microRNA-25 Inhibits Cell Apoptosis of Human Gastric Adenocarcinoma Cell Line AGS via Regulating CCNE1 and MYC

Yong ZhangBCDE, Zheng PengBCD, Yunshan ZhaoBCDE, Lin ChenAEFG

DOI: 10.12659/MSM.896118

Med Sci Monit 2016; 22:1415-1420


BACKGROUND: Gastric carcinoma is the second leading cause of cancer death. microRNAs play vital roles in regulating expression of related oncogenes. microRNA-25 (miR-25) has been found to be up-regulated in gastric carcinoma. However, its roles in affecting cell apoptosis of gastric carcinoma and the related mechanism remain elusive. This study aimed to uncover the influences of miR-25 on gastric carcinoma cell apoptosis and the possible functional mechanisms involved.

MATERIAL AND METHODS: Human gastric adenocarcinoma cell line AGS was used and transfected with lentivirus containing miR-25-specifc inhibitor sponge or expression vector to analyze the effects of miR-25.

RESULTS: miR-25 had higher expression in AGS than in human gastric epithelial cell line GES-1 (P<0.01). Inhibition of miR-25 by its sponge in AGS cells resulted in suppressed cell viability (P<0.01) and promoted cell apoptosis (P<0.01), while overexpression of miR-25 abrogated these effects (P<0.01 and P<0.05), indicating that miR-25 can promote cell viability and inhibit cell apoptosis in AGS cells. Expression analysis of related factors by Western blot showed that inhibiting miR-25 led to the up-regulation of F-box and WD repeat domain-containing 7 (FBXW7, P<0.01) and the down-regulation of FBXW7 substrates, cyclin E1 (CCNE1, P<0.01), and v-myc avian myelocytomatosis viral oncogene homolog (MYC, P<0.001).

CONCLUSIONS: These results indicate that miR-25 has anti-apoptosis roles in AGS cells, possibly via inhibiting FBXW7 and thus promoting oncogenes, such as CCNE1 and MYC. This study provides basic evidence for using miR-25 as a possible therapeutic target in treating gastric carcinoma.

Keywords: Apoptosis - genetics, Adenocarcinoma - pathology, Cell Cycle Proteins - metabolism, Cell Survival - genetics, Cyclin E - metabolism, Epithelial Cells - pathology, F-Box Proteins - metabolism, Oncogene Proteins - metabolism, Proto-Oncogene Proteins c-myc - metabolism, Ubiquitin-Protein Ligases - metabolism, Up-Regulation - genetics



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Nahum Mendez-Sanchez, Shreya C. Pal
Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico

DOI: 10.12659/MSM.937371

Med Sci Monit 2022; 28:e937371


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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750