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Journal of Cancer Research and Clinical Oncology

, Volume 138, Issue 10, pp 1781–1788 | Cite as

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

  • Zhiwei Zhong
  • Zhuo Dong
  • Lihua Yang
  • Zhaohui GongEmail author
Rapid Communication

Abstract

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.

Keywords

miR-21 Mismatch repair Human mutS homolog 2 (hMSH2) Cell cycle Lung cancer 

Notes

Acknowledgments

We are grateful to Mrs Qiong Liu for her technical assistance in flow cytometry and Dr. Junming Guo for his critical suggestions on the manuscript. This work was supported by research grants from the Key Scientific Research Fund of Zhejiang Provincial Education Department (Z201119414), the Natural Science Foundation of Zhejiang Province (LY12C06002), the Scientific Innovation Team Projects of Ningbo and Zhejiang Education Department (2011B82014, T200907), the Scientific Research Foundation of Graduate School of Ningbo University (G11JA007), and the K.C.Wong Magna Fund at Ningbo University.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Zhiwei Zhong
    • 1
  • Zhuo Dong
    • 1
  • Lihua Yang
    • 1
  • Zhaohui Gong
    • 1
    Email author
  1. 1.Institute of Biochemistry and Molecular Biology, School of MedicineNingbo UniversityNingboChina

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