microRNA-25 Inhibits Cell Apoptosis of Human Gastric Adenocarcinoma Cell Line AGS via Regulating CCNE1 and MYC.
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.
Department of Genernal Surgery, General Hospital of Chinese PLA, Beijing, China (mainland).
Yong
Y
Zhang
Department of Genernal Surgery, General Hospital of Chinese PLA, Beijing, China (mainland).
Zheng
Z
Peng
Department of Genernal Surgery, General Hospital of Chinese PLA, Beijing, China (mainland).
Yunshan
Y
Zhao
Department of Genernal Surgery, General Hospital of Chinese PLA, Beijing, China (mainland).
Lin
L
Chen
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
C475820:CCNE1 protein, human; D018797:Cell Cycle Proteins; D019927:Cyclin E; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C543351:MIRN25 microRNA, human; D035683:MicroRNAs; D015513:Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D044767:Ubiquitin-Protein Ligases