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J Cancer Res Clin Oncol. 2012 Oct;138(10):1781-8. Epub 2012 Jul 18.

miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer.

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Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, 818 Fenghua Road, Ningbo 315211, China.



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.


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.


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.


These data suggest miR-21 is a key regulator of hMSH2 and modulates cell cycle and proliferation by targeting hMSH2 in human lung cancer.

[Indexed for MEDLINE]

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