Interleukin-17A mediates tobacco smoke–induced lung cancer epithelial-mesenchymal transition through transcriptional regulation of ΔNp63α on miR-19
Authors: Xiaoqian Wang
Chunfeng Xie
Caiyun Zhong
Jianyun Zhu
Yu Meng
Zili Meng
Hongbin Shen
Cong Huang
Shanshan Geng
Zhibin Hu
Jieshu Wu
Xue Yang
Xiaoting Li
Journal: Cell Biology and Toxicology (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Epithelial-mesenchymal transition; IL-17A; Lung cancer; Tobacco smoke; ΔNp63α/miR-19.
Affiliations: Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China., Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215008, Jiangsu, China., Guangde Center for Diseases Prevention and Control, Guangde, 242200, Anhui, China., Department of Clinical Nutrition, Nanjing Drum Tower Hospital, Nanjing, 211166, Jiangsu, China., Wuxi Center for Disease Control and Prevention, The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi, 214023, Jiangsu, China., Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211126, China., Collaborative Innovation Center for Cancer Personalized Medicine, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center, Nanjing Medical University, Nanjing, 211126, China., Department of Respiratory Medicine, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, 223300, Jiangsu, China. ., Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. ., Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China. .

Abstract:  Interleukin-17A (IL-17A) is an essential inflammatory cytokine in the progress of carcinogenesis. Tobacco smoke (TS) is a major risk factor of lung cancer that influences epithelial-mesenchymal transition (EMT) process. However, the potential mechanism by which IL-17A mediates the progression of lung cancer in TS-induced EMT remains elusive. In the present study, it was revealed that the IL-17A level was elevated in lung cancer tissues, especially in tumor tissues of cases with experience of smoking, and a higher IL-17A level was correlated with induction of EMT in those specimens. Moreover, the expression of ΔNp63α was increased in IL-17A-stimulated lung cancer cells. ΔNp63α functioned as a key oncogene that bound to the miR-17-92 cluster promoter and transcriptionally increased the expression of miR-19 in lung cancer cells. Overexpression of miR-19 promoted EMT in lung cancer with downregulation of E-cadherin and upregulation of N-cadherin, while its inhibition suppressed EMT. Finally, the upregulated levels of IL-17A, ΔNp63α, and miR-19 along with the alteration of EMT-associated biomarkers were found in lung tissues of TS-exposed mice. Taken together, the abovementioned results suggest that IL-17A increases ΔNp63α expression, transcriptionally elevates miR-19 expression, and promotes TS-induced EMT in lung cancer. These findings may provide a new insight for the identification of therapeutic targets for lung cancer. 

Retracted: No

PubPeer comments:
 In the **Data Availability**, the authors wrote: Data and materials are available and transparent. It is confusing because there is no supplementary material in this article. , 
 We are sorry for this confusing. Our statement means that all data and materials are included in this paper. There is no supplementary materials in this article. Thanks for pointing this out! , 
 #1 We are sorry for this confusing. Our statement means that all data and materials are included in this paper. There is no supplementary materials in this article. Thanks for pointing this out! ,