MicroRNA-181a functions as an oncomir in gastric cancer by targeting the tumour suppressor gene ATM.

Abstract

Based on our previous experiments, this study is to further investigate the functional significance of miR-181a and its target gene in gastric cancer. Expression of miR-181a was detected by qRT-PCR in three normal gastric tissues and three human gastric cancer cell lines (SGC-7901, MGC-803, and BGC-823 cells). After transfection with miR-181a inhibitor, proliferation, apoptosis, migration, and invasion of the SGC-7901 cells were evaluated. Ataxia-telangiectasia mutation (ATM) was predicted as a target gene of miR-181a with bioinformatics analysis, and was verified by lucifersae reporter assay. Expression of ATM protein in HEK293T cells and tissues was measured by Western Blot. Expression of ATM mRNA in HEK293T cells was measured by RT-PCR. Compared with three non-tumour tissues, the expression of miR-181a in three gastric cancer cells was significantly increased by 26.68, 14.83 and 14.96 folds; Compared with Negative Control(NC) and blank groups, transfection of miR-181a inhibitor led to inhibition of SGC7901 cell proliferation, invasion, and migration as well as promotion of apoptosis. A luciferase reporter assay demonstrated that ATM was a direct target of miR-181a, miR-181a mimics transfection down regulated ATM mRNA and protein expression. There was inverse correlation between miR-181a and ATM protein expression in gastric cancer and normal gastric tissues. Our study demonstrates that over-expression of miR-181a might be involved in development of gastric cancer by promoting proliferation and inhibiting apoptosis probably through directly targeting ATM. miR-181a modulation may be a potential strategy for the development of miRNA-based therapy of gastric cancer.

• Authors: Xiangyang Zhang, Yuqiang Nie, Xiaorong Li, Guifu Wu, Qun Huang, Jie Cao, Yanlei Du, Junda Li, Ruoyu Deng, Dongshen Huang, Baozhi Chen, Shang Li, Baojun Wei
• Journal: Pathology oncology research : POR (Pathol Oncol Res) Vol. 20 Issue 2 Pg. 381-9 (Apr 2014) ISSN: 1532-2807 [Electronic] Switzerland
• PMID: 24531888 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIrn181 microRNA, human
• MicroRNAs
• RNA, Messenger
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins

Topics

• Apoptosis (genetics)
• Ataxia Telangiectasia Mutated Proteins (genetics)
• Cell Line
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Computational Biology (methods)
• Down-Regulation (genetics)
• Gene Expression Regulation, Neoplastic (genetics)
• Genes, Tumor Suppressor (physiology)
• HEK293 Cells
• Humans
• MicroRNAs (genetics)
• Neoplasm Invasiveness (genetics)
• RNA, Messenger (genetics)
• Stomach Neoplasms (genetics)
• Transfection (methods)