TY - JOUR
T1 - TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression
AU - Xie, Chunfeng
AU - Zhu, Jianyun
AU - Yang, Xue
AU - Huang, Cong
AU - Zhou, Liping
AU - Meng, Zili
AU - Li, Xiaoting
AU - Zhong, Caiyun
N1 - Funding Information:
This work was supported by the grants from the National Basic Research Program of China (973 Program) (No. 2013CB910303), the National Natural Science Foundation of China (Nos. 81803210, 81773431, and 81573139), the Natural Science Foundation of Jiangsu Province (BK20180217), and the China Postdoctoral Science Foundation Funded Project (Nos. 2018M642280 and 2020T130312).
Publisher Copyright:
© Copyright © 2021 Xie, Zhu, Yang, Huang, Zhou, Meng, Li and Zhong.
PY - 2021/3/4
Y1 - 2021/3/4
N2 - As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.
AB - As a key risk factor for lung cancer, tobacco smoke (TS) influences several cellular processes, including epithelial-mesenchymal transition (EMT). TAp63α is a crucial transcription factor involved in tumor progression. The present study was designed to investigate the potential role and underlying mechanisms of TAp63α in TS-induced lung cancer EMT. We found that compared to normal tissues, the tumor tissues collected from lung cancer patients showed a lower level of TAp63α expression, along with downregulated E-cadherin expression and upregulated Vimentin expression. Results of treatment with TAp63α and TAp63α siRNA as well as with tumor growth factor-β (TGF-β) showed that TAp63α acted as a tumor suppressor gene, and its upregulated expression suppressed lung cancer EMT. Significantly, TS exposure altered expression of EMT-related markers, enhanced cell migratory and invasive capacities, and decreased the TAp63α expression level in lung cancer cells. Overexpression of TAp63α significantly alleviated TS-stimulated lung cancer EMT. Mechanistically, TAp63α expression transcriptionally reduced the miR-19 level, which resulted in the suppression of lung cancer EMT. Additionally, as a natural compound possessing anti-cancer effects, curcumin inhibited TS-induced lung cancer EMT by increasing TAp63α expression and reducing miR-19 expression. Collectively, our results indicate that TAp63α inhibits TS-induced lung cancer EMT via transcriptionally suppressing miR-19 and the inhibitory effect of TAp63α on miR-19 mediates the anti-cancer action of curcumin. These findings provide new insights into novel targets for lung cancer prevention.
KW - curcumin
KW - EMT
KW - lung cancer
KW - miR-19
KW - TAp63α
KW - tobacco smoke
UR - http://www.scopus.com/inward/record.url?scp=85102795262&partnerID=8YFLogxK
U2 - 10.3389/fcell.2021.645402
DO - 10.3389/fcell.2021.645402
M3 - Journal article
AN - SCOPUS:85102795262
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 645402
ER -