Inhibition of TMEM16A suppresses growth and induces apoptosis in hepatocellular carcinoma
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ORIGINAL ARTICLE
Inhibition of TMEM16A suppresses growth and induces apoptosis in hepatocellular carcinoma Chuantao Zhang1 · Jianxiang Liu2 · Zhiyi Han3 · Xiang Cui3 · Deti Peng3 · Yufeng Xing3 Received: 5 August 2019 / Accepted: 3 March 2020 © Japan Society of Clinical Oncology 2020
Abstract Background Increase of the C a2+-activated chloride channel TMEM16A is contribute to tumorigenesis. However, the expression level of TMEM16A and its underlying molecular mechanism for TMEM16Apromotingliver carcinogenesis is remains unknown. Methods In the present study, the expression of TMEM16A in hepatocellular carcinoma (HCC) tissues were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot and immunohistochemical. Cell proliferation was detected using CCK-8, EdU staining and colony formation methods. Flow cytometry was carried out for detecting cell cycle distribution and apoptosis rate. Migration and invasion abilities were analyzed using transwell and wound healing assay. Western blot method was performed to analyze protein expression. Results Here, we found TMEM16A was significantly increased in HCC tissues, and a higher TMEM16A expression levels were detected in larger tumor size, higher tumor grade, with distant metastasis and poor differentiation. Moreover, overexpression of TMEM16A promoted HCC growth, migration and invasion, and suppressed apoptosis in vitro and in vivo. Knockdown of TMEM16A inhibited HCC growth, migration and invasion, and induced apoptosis in vitro and in vivo. Furthermore, TMEM16A regulated PI3K/AKT-MAKP signaling pathway. Conclusion Our data indicate that TMEM16A may represent a novel biomarker of HCC and may be a potential therapeutic target for diagnosis and therapy. Keywords TMEM16A · HCC · PI3K/AKT-MAKP · Cell proliferation · Tumorigenesis
Introduction Hepatocellular carcinoma (HCC) is the major type of liver cancer with high morbidity and mortality in patients [1]. HCC is currently the third leading cause of tumor-associated deaths all over the world, and causing 466 thousand new Chuantao Zhang and Jianxiang Liu contributed equally to this work. * Yufeng Xing [email protected]; [email protected] 1
Department of Respiration, Hospital of Chengdu university of Traditional Chinese Medicine, Chengdu 610072, Sichuan, China
2
Key Laboratory of Medicinal Biotechnology, Guilin Medical University, Guilin 541004, Guangxi, China
3
Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, NO.1, Fuhua Road, Futian District, Shenzhen 518033, Guangdong, China
incidences and more than 122 thousand deaths in China [2]. Although the molecular mechanisms of underlying HCC have been greatly uncovered, patients are suffered with high rate of tumor recurrence and metastasis [3]. Because of most HCC patients are diagnosed at advantaged stages, great advances in diagnosis and therapeutic strategies in HCC, including surgery, chemotherapy, and radiation still have limitation [4], and the 5-year survival rate of HCC patients i
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