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Mdig, a lung cancer-associated gene, regulates cell cycle progression through p27KIP1

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Tumor Biology

Abstract

Mineral dust-induced gene (mdig) can accelerate cell proliferation. The aim of this study is to investigate the mechanism by which mdig regulates cell proliferation. A549 cells were transfected with siRNA specifically targeting mdig. Cell proliferation and cell cycle progression were measured using MTT assay and cell cycle analysis, respectively. Furthermore, real-time reverse transcription quantitative–polymerase chain reaction (RT-qPCR) was performed in A549 cells transfected with mdig siRNA to examine the expression levels of the cell cycle related genes such as p18INK4c, p19INK4d, p21WAF/CIP1, p27KIP1, p57KIP2, cyclin D1, and cyclin E. To further explore the effect of mdig on p27KIP1, the expression levels of total p27KIP1 and its subtypes pT187-p27KIP1 and pS10-p27KIP1 were assessed by Western blotting. In vivo, Western blotting was performed to check the expression levels of mdig and p27KIP1 in human lung cancer tissues, para-cancerous normal lung tissues, and para-bronchial stumps. Knockdown of mdig induced increases in p27KIP1, both on mRNA and protein levels. Furthermore, the phosphorylation of p27KIP1 at its Thr187 site was also inhibited. Importantly, in lung cancer tissues, upregulation of mdig expression accompanies with the downregulation of p27KIP1 expression and in bronchial stump, vice versa. The data suggest that mdig-mediated inhibition of p27KIP1 is important for cell proliferation and tumor formation and reveal therapeutic potential of p27KIP1 for lung cancer.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No.: 81472194) and Bureau of Science and Technology of Shenyang (Grant No.: F12-193-9-02) to Hongwen Zhao.

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Authors and Affiliations

  1. Department of Pulmonary Medicine, The First Hospital of China Medical University, Shenyang, 110001, China

    Dan Ma, Dan Guo, Wei Li & Hongwen Zhao

  2. Department of Pulmonary Medicine, The Fourth Hospital of China Medical University, Shenyang, 110032, China

    Dan Ma

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  1. Dan Ma
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  2. Dan Guo
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  3. Wei Li
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  4. Hongwen Zhao
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Correspondence to Hongwen Zhao.

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Ma, D., Guo, D., Li, W. et al. Mdig, a lung cancer-associated gene, regulates cell cycle progression through p27KIP1 . Tumor Biol. 36, 6909–6917 (2015). https://doi.org/10.1007/s13277-015-3397-z

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  • DOI: https://doi.org/10.1007/s13277-015-3397-z

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