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TMEM166 inhibits cell proliferation, migration and invasion in hepatocellular carcinoma via upregulating TP53

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Abstract

Transmembrane protein 166 (TMEM166), an endoplasmic reticulum-associated protein, functions in many diseases via regulating autophagy and/or apoptosis. However, the role of TMEM166 in hepatocellular carcinoma (HCC) remains largely unknown. In this study, we detected the expression of TMEM166 in HCC by real-time fluorescent quantitative PCR (RT-qPCR), immunohistochemistry and western blot. To investigate its biological function and underlying mechanism in HCC, TMEM166 was overexpressed in HCC cell lines and assessed its effects on cell proliferation, migration, invasion, apoptosis and cell cycle by MTT assay, wound healing assay, Transwell assay, Annexin V-FITC/PI assay, JC-1 staining and flow cytometry assay, respectively. Results demonstrated that the expression of TMEM166 was significantly decreased in HCC and was associated with advanced TNM clinical stage and poor clinical outcome of HCC patients. TMEM166 overexpression inhibited HCC cells proliferation, migration and invasion. Furthermore, TMEM166 inhibited cell proliferation by inducing apoptosis and cell cycle arrest via upregulating anti-oncogene TP53 and TP53 knockdown significantly alleviated the anti-tumor effects of TMEM166 on HCC cells. This study provides the first comprehensive analysis the role of TMEM166 in HCC. TMEM166 displays a fine anti-tumor activity on HCC cells involving a mechanism of upregulating TP53. This study suggests TMEM166 is a potential target for the treatment of HCC.

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Acknowledgements

We thank Prof. Yingyu Chen from Peking University Health Science Center for providing us with TMEM166 plasmid. This work was supported by China Postdoctoral Science Foundation Special Funding Project (Grant Number 2016T90612); China Postdoctoral Science Foundation Funded Project (Grant Number 2015M57074) and Qingdao Applied Basic Research Program Youth Project (Grant Number 19-6-2-59-cg).

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Author notes

  1. Jiejie Yang and Bin Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China

    Jiejie Yang, Qian Xu, Lin Hou, Kan Yin, Yixuan Li, Jinyu Zhang & Ning Li

  2. School of Electronic Information, Qingdao University, Qingdao, 266071, China

    Bin Wang

  3. Department of Infectious Diseases, Affiliated Hospital of Qingdao University, Qingdao, 266000, China

    Yuling Yang

  4. Biotherapy Center, Clinical Laboratory, Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, 266042, China

    Qingming Guo

  5. Department of Neurobiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China

    Yanan Hua

  6. Experimental Center for Undergraduates of Pharmacy, School of Pharmacy, Qingdao University, Qingdao, 266021, China

    Li Zhang

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  1. Jiejie Yang
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Correspondence to Ning Li.

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Yang, J., Wang, B., Xu, Q. et al. TMEM166 inhibits cell proliferation, migration and invasion in hepatocellular carcinoma via upregulating TP53. Mol Cell Biochem 476, 1151–1163 (2021). https://doi.org/10.1007/s11010-020-03979-1

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  • DOI: https://doi.org/10.1007/s11010-020-03979-1

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