Inhibition of TMEM16A suppresses growth and induces apoptosis in hepatocellular carcinoma.

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.

journal_name

Int J Clin Oncol

authors

Zhang C,Liu J,Han Z,Cui X,Peng D,Xing Y

doi

10.1007/s10147-020-01653-6

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

1145-1154

issue

6

eissn

1341-9625

issn

1437-7772

pii

10.1007/s10147-020-01653-6

journal_volume

25

pub_type

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