TMEM166 inhibits cell proliferation, migration and invasion in hepatocellular carcinoma via upregulating TP53
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TMEM166 inhibits cell proliferation, migration and invasion in hepatocellular carcinoma via upregulating TP53 Jiejie Yang1 · Bin Wang2 · Qian Xu1 · Yuling Yang3 · Lin Hou1 · Kan Yin1 · Qingming Guo4 · Yanan Hua5 · Li Zhang6 · Yixuan Li1 · Jinyu Zhang1 · Ning Li1 Received: 8 July 2020 / Accepted: 6 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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 (RTqPCR), 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 antitumor 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. Keywords TMEM166 · Hepatocellular carcinoma (HCC) · Apoptosis · TP53
Introduction Hepatocellular carcinoma (HCC), the most common primary malignancy of the liver, is considered to be the fourth leading cause of cancer-related death worldwide in 2018 [1, 2]. Jiejie Yang and Bin Wang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03979-1) contains supplementary material, which is available to authorized users. * Ning Li ning‑[email protected] 1
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao 266071, China
2
School of Electronic Information, Qingdao University, Qingdao 266071, China
3
Department of Infectious Diseases, Affiliated Hospital of Qingdao University, Qingdao 266000, China
There are about 841,000 new cases of HCC worldwide each year, with a mortality rate of 70% and an overall 5-year survival rate of 10.1% [3]. Although significant improvements have been made in the diagnosis and effective monitoring for HCC in recent years, the prognosis of HCC remains unsatisfactory, since it is often diagnosed at an advanced stage.
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