Cong Hu1, Ronggui Zhang2, Depeng Jiang3. 1. Department of Intensive Care, Zhuhai People's Hospital, The Third Affiliated Hospital, Jinan University, Zhuhai, 519000, China. 2. Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China. 3. Department of Respiratory Medicine, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
Abstract
BACKGROUND: Transmembrane 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. METHODS: qRT-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. RESULTS: Our 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. CONCLUSION: TMEM16A 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.
BACKGROUND:Transmembrane 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. METHODS: qRT-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 micecancer tissues. RESULTS: Our 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. CONCLUSION:TMEM16A 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.
Authors: Kristina Jansen; Martina Kluth; Niclas C Blessin; Claudia Hube-Magg; Michael Neipp; Hamid Mofid; Hannes Lárusson; Thies Daniels; Christoph Isbert; Stephan Coerper; Daniel Ditterich; Holger Rupprecht; Albert Goetz; Christian Bernreuther; Guido Sauter; Ria Uhlig; Waldemar Wilczak; Ronald Simon; Stefan Steurer; Eike Burandt; Daniel Perez; Jakob R Izbicki; Frank Jacobsen; Till S Clauditz; Andreas H Marx; Till Krech Journal: Histol Histopathol Date: 2022-06-01 Impact factor: 2.130
Authors: Kristina Jansen; Franziska Büscheck; Katharina Moeller; Martina Kluth; Claudia Hube-Magg; Niclas Christian Blessin; Daniel Perez; Jakob Izbicki; Michael Neipp; Hamid Mofid; Thies Daniels; Ulf Nahrstedt; Christoph Fraune; Frank Jacobsen; Christian Bernreuther; Patrick Lebok; Guido Sauter; Ria Uhlig; Waldemar Wilczak; Ronald Simon; Stefan Steurer; Eike Burandt; Andreas Marx; Till Krech; Till Clauditz Journal: PeerJ Date: 2021-08-03 Impact factor: 2.984
Authors: Mi Ran Choi; Hae Dong Kim; Sinyoung Cho; Seong Ho Jeon; Dong Hyun Kim; Jungwon Wee; Young Duk Yang Journal: Int J Mol Sci Date: 2021-07-01 Impact factor: 5.923