Journal
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
Volume 138, Issue 10, Pages 1781-1788Publisher
SPRINGER
DOI: 10.1007/s00432-012-1287-y
Keywords
miR-21; Mismatch repair; Human mutS homolog 2 (hMSH2); Cell cycle; Lung cancer
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Funding
- Zhejiang Provincial Education Department [Z201119414]
- Natural Science Foundation of Zhejiang Province [LY12C06002]
- Scientific Innovation Team Projects of Ningbo and Zhejiang Education Department [2011B82014, T200907]
- Scientific Research Foundation of Graduate School of Ningbo University [G11JA007]
- K.C. Wong Magna Fund at Ningbo University
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Purpose MicroRNAs regulate critical genes associated with lung cancer. Human mutS homolog 2 (hMSH2), one of the core mismatch repair genes, is affected in lung cancer development. The aim of this study is to investigate the role of miR-21 in hMSH2 gene expression and the effect of miR-21 on cell proliferation and cell cycle in lung cancer. Methods The targets of miR-21 were predicted by a bioinformatics tool, and hMSH2 was validated as a direct target of miR-21 by luciferase activity assay. MiRNA mimics or inhibitors were used to stimulate or attenuate the effect of endogenous miR-21 on hMSH2 expression. MiR-21 and hMSH2 expressions were assessed with real-time RT-PCR and Western blotting. Cell cycle was determined by flow cytometry, and cell growth was analyzed by MTT assay and real-time cell analysis system. Results MiR-21 expression was inversely correlated with hMSH2 expression in human lung cancer cell lines. Further validation showed hMSH2 was directly regulated by miR-21. The up-regulation of miR-21 significantly promoted cell proliferation and revealed a higher proportion of cells at S phase. However, knockdown of miR-21 expression resulted in cell cycle arrest at G2/M phase and inhibited cell proliferation. Conclusions These data suggest miR-21 is a key regulator of hMSH2 and modulates cell cycle and proliferation by targeting hMSH2 in human lung cancer.
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