• Cong Hu, Ronggui Zhang, and Depeng Jiang.
• Department of Intensive Care, Zhuhai People's Hospital, The Third Affiliated Hospital, Jinan University, Zhuhai, 519000, China.
• Arch Iran Med. 2019 Jan 1; 22 (1): 32-38.

BackgroundTransmembrane protein 16A (TMEM16A), also known as ANO1 (anoctamin-1), was reported to be vital in the growth and invasion of several malignancies. However, role of TMEM16A in lung cancer remained unclear. The aim of this study was to evaluate the expression of TMEM16A and its significance in lung cancer.MethodsqRT-PCR and Western blots were performed to evaluate the TMEM16A mRNA and protein expression. Proliferation and invasion of H1299 cancer cells were evaluated by CCK-8 and transwell assays. Tumor volumes in nude mice implanted with H1299 cells were assessed once every week for 5 weeks by measuring 2 perpendicular dimensions. Immunofluorescent staining revealed expression of TMEM16A in nude mice cancer tissues.ResultsOur findings provided compelling evidence that TMEM16A production in H1299 cells is 2.1 times higher than observations in HBE16 cells. We showed that overexpression of TMEM16A contributed to the proliferation of H1299 cells. Moreover, T16Ainh-A01, a specific TMEM16A inhibitor or shRNA targeting TMEM16A somewhat inhibited lung tumor cell growth and invasion as evident from in vitro studies and from in vivo xenograft-tumor growth. Inhibition of TMEM16A strongly suppressed EGFR phosphorylation and growth of lung cancer cells. Furthermore, a reduction of p-RAS and p-ERK1/2 was also observed.ConclusionTMEM16A promoted growth and invasion in lung cancer cells via an EGFR/ MAPK-dependent signaling pathway. So we infer TMEM16A membrane protein may have potential to serve as a biomarker in lung cancer.© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

40 keywords...

hide…