Chuantao Zhang1, Jianxiang Liu2, Zhiyi Han3, Xiang Cui3, Deti Peng3, Yufeng Xing4. 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. 4. Department of Hepatology, Shenzhen Traditional Chinese Medicine Hospital, NO.1, Fuhua Road, Futian District, Shenzhen, 518033, Guangdong, China. yufeng000729@163.com.
Abstract
BACKGROUND: Increase of the Ca2+-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.
BACKGROUND: Increase of the Ca2+-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.
Authors: Adrian Britschgi; Anke Bill; Heike Brinkhaus; Christopher Rothwell; Ieuan Clay; Stephan Duss; Michael Rebhan; Pichai Raman; Chantale T Guy; Kristie Wetzel; Elizabeth George; M Oana Popa; Sarah Lilley; Hedaythul Choudhury; Martin Gosling; Louis Wang; Stephanie Fitzgerald; Jason Borawski; Jonathan Baffoe; Mark Labow; L Alex Gaither; Mohamed Bentires-Alj Journal: Proc Natl Acad Sci U S A Date: 2013-02-19 Impact factor: 11.205
Authors: Fen Huang; Jason R Rock; Brian D Harfe; Tong Cheng; Xiaozhu Huang; Yuh Nung Jan; Lily Yeh Jan Journal: Proc Natl Acad Sci U S A Date: 2009-11-24 Impact factor: 11.205