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MicroRNA-31-5p modulates cell cycle by targeting human mutL homolog 1 in human cancer cells

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Tumor Biology

Abstract

MicroRNAs (miRNAs) and DNA mismatch repair (MMR) have been linked to human cancer progression. Human mutL homolog 1 (hMLH1), one of the core MMR genes, defects in lung cancer development. However, the interaction between miRNAs and MMR genes and their regulatory effect on cell cycle remain poorly understood. In this study, we investigated the role of miR-31-5p in hMLH1 gene expression and the effect of miR-31-5p on cell cycle in non-small cell lung cancer (NSCLC). We found that miR-31-5p was inversely correlated with hMLH1 expression in NSCLC cell lines and hMLH1 was a direct target of miR-31-5p. Knockdown of miR-31-5p induced a cell cycle arrest at G2/M phase and increased hMLH1 protein expression in NSCLC cells. Conversely, overexpression of miR-31-5p significantly induced cell cycle arrest at S phase and decreased hMLH1 protein expression. Furthermore, knockdown of hMLH1 upregulated miR-31-5p expression and caused cell cycle arrest at S phase. Data from this study revealed that miR-31-5p modulates cell cycle by targeting hMLH1 protein at the posttranscriptional level in NSCLC, which may represent a novel therapy strategy for lung cancer by targeting miR-31-5p.

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Acknowledgments

We are grateful to Mrs. Qiong Liu (Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University) for her technical assistance in flow cytometry and Dr. Jinghai Chen (Department of Cardiology, Children’s Hospital Boston, Harvard Medical School) 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 Natural Science Foundation of Ningbo City (2012A610193), the Scientific Innovation Team Project of Ningbo (2011B82014), the Scientific Research Foundation of Graduate School of Ningbo University (G11JA007 and G12JA015), and the K.C. Wong Magna Fund at Ningbo University.

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Authors and Affiliations

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

    Zhiwei Zhong, Zhuo Dong, Lihua Yang & Zhaohui Gong

  2. Clinical Research Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310035, China

    Zhiwei Zhong

  3. College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China

    Xiaoqiang Chen

  4. Hubei University of Technology, Wuhan, China

    Xiaoqiang Chen

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  1. Zhiwei Zhong
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  2. Zhuo Dong
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  3. Lihua Yang
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  4. Xiaoqiang Chen
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  5. Zhaohui Gong
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Correspondence to Xiaoqiang Chen or Zhaohui Gong.

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Zhong, Z., Dong, Z., Yang, L. et al. MicroRNA-31-5p modulates cell cycle by targeting human mutL homolog 1 in human cancer cells. Tumor Biol. 34, 1959–1965 (2013). https://doi.org/10.1007/s13277-013-0741-z

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  • DOI: https://doi.org/10.1007/s13277-013-0741-z

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