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MiR-183 inhibits invasion of gastric cancer by targeting Ezrin.

ABSTRACT: miR-183, a member of an evolutionarily conserved miRNA cluster (miR-96, miR-182, and miR-183), has been demonstrated to act as both a tumor suppressor and oncogene in various type of human cancer. However, the biological role of miR-183 in gastric cancer (GC) still remains unclear. In the present study, miR-183 expression was significantly decreased in gastric cancer tissues compared with its' adjacent normal tissues, and down-regulation of miR-183 was significantly associated with lymph node metastasis and pathological TNM stage. Furthermore, Erzin, which was reported to be up-regulated in gastric cancer, was identified as an efficient target of miR-183. Overexpression of miR-183 markedly suppressed cells invasion by downregulation of Ezrin expression. However, miR-183 expression didn't affect cells proliferation and cell cycle distribution of GC. In conclusion, our study demonstrated that miR-183 acts as a tumor suppressor in GC, partially at least via regulation of Ezrin. Therefore, miR-183 may be a potential target for the treatment of gastric cancer.

SUBMITTER: Cao LL

PROVIDER: S-EPMC4203171 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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miR-183 inhibits invasion of gastric cancer by targeting Ezrin.

Cao Long-Long LL Xie Jian-Wei JW Lin Yao Y Zheng Chao-Hui CH Li Ping P Wang Jia-Bin JB Lin Jian-Xian JX Lu Jun J Chen Qi-Yue QY Huang Chang-Ming CM

International journal of clinical and experimental pathology 20140815 9

miR-183, a member of an evolutionarily conserved miRNA cluster (miR-96, miR-182, and miR-183), has been demonstrated to act as both a tumor suppressor and oncogene in various type of human cancer. However, the biological role of miR-183 in gastric cancer (GC) still remains unclear. In the present study, miR-183 expression was significantly decreased in gastric cancer tissues compared with its' adjacent normal tissues, and down-regulation of miR-183 was significantly associated with lymph node me ...[more]

PMID: 25337200

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Project description:BackgroundThe involvement of miRNAs in the regulation of fundamental cellular functions has placed them at the fore of ongoing investigations into the processes underlying carcinogenesis. MiRNA expression patterns have been shown to be dysregulated in numerous human malignancies, including breast cancer, suggesting their probable involvement as novel classes of oncogenes or tumour suppressor genes. The identification of differentially expressed miRNAs and elucidation of their functional roles may provide insight into the complex and diverse molecular mechanisms of tumorigenesis. MiR-183 is located on chromosome 7q32 and is part of a miRNA family which are dysregulated in numerous cancers. The aims of this study were to further examine the expression and functional role of miR-183 in breast cancer.MethodsMiR-183 expression was quantitated in primary breast tumours, tumour associated normal tissue and breast cancer cell lines using RQ-PCR. Gain of function analysis was performed in breast cancer cells using pre-miR-183 and the effect of miR-183 overexpression on cell viability, proliferation, apoptosis and migration was examined. Customized Taqman Low Density Arrays (TLDA) were used to identify dysregulated genes in breast cancer cells transfected with pre-miR-183.ResultsWe demonstrate that miR-183 is dysregulated in breast cancer and expression correlates with estrogen receptor and HER2/neu receptor expression. Induced overexpression of miR-183 inhibited migration of breast cancer cells. This finding was substantiated by RQ-PCR of mRNA from cells overexpressing miR-183 which showed dysregulation of several migration and invasion related genes. Specifically, the VIL2-coding protein Ezrin was confirmed as a target of miR-183 and downregulation of this protein was confirmed with immunocytochemistry.ConclusionsThese findings indicate that miR-183 targets VIL2 and may play a central role in the regulation of migration and metastasis in breast cancer. Consequently, this miRNA may present an attractive target for therapeutic intervention.

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MiR-183 inhibits invasion of gastric cancer by targeting Ezrin.

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miR-183 inhibits invasion of gastric cancer by targeting Ezrin.

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