TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression.
TAp63α Is Involved in Tobacco Smoke-Induced Lung Cancer EMT and the Anti-cancer Activity of Curcumin via miR-19 Transcriptional Suppression.
复制标题
TAp63 α 参与烟草烟雾诱导的肺癌 EMT 以及姜黄素通过 miR-19 转录抑制的抗癌活性
DOI：
10.3389/fcell.2021.645402
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Zhong C
中科院分区：
文献类型：
--
作者：
Xie C;Zhu J;Yang X;Huang C;Zhou L;Meng Z;Li X;Zhong C
烟草烟雾(TS)作为肺癌的关键危险因素，影响着多种细胞过程，包括上皮-间充质转化(EMT)。TAp63α是参与肿瘤进展的重要转录因子。本研究旨在探讨TAp63α在TS诱导的肺癌EMT中的作用及其机制。我们发现，与正常组织相比，肺癌患者的肿瘤组织中TAp63mRNA的表达水平较低，E-钙粘附素的表达下调，波形蛋白的表达上调。TAp63α和TAp63αsiRNA以及肿瘤生长因子-β(TGFR-β)的作用结果表明，TAp63α具有抑癌基因的作用，其上调表达抑制了肺癌的EMT。显著地，TS暴露改变了肺癌细胞中EMT相关标志物的表达，增强了细胞的迁移和侵袭能力，并降低了TAp63α的表达水平。过表达TAp63α可显著减轻TS刺激的肺癌细胞转移率。从机制上讲，TAp63α的表达下调了miR-19的表达水平，从而抑制了肺癌细胞间的转移。此外，姜黄素作为一种具有抗癌作用的天然化合物，可通过上调TAp63α的表达和下调miR-19的表达来抑制TS诱导的肺癌内皮细胞转移。综上所述，我们的结果表明TAp63α通过转录抑制miR-19来抑制TS诱导的肺癌EMT，并且TAp63α对miR-19的抑制作用介导了姜黄素的抗癌作用。这些发现为肺癌预防的新靶点提供了新的见解。
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.
登录
查看更多内容
影响因子：
20.4
作者：
Lo Iacono, Marco;Monica, Valentina;Scagliotti, Giorgio V.
通讯作者：
Scagliotti, Giorgio V.
影响因子：
11.2
作者：
Pillai S;Trevino J;Rawal B;Singh S;Kovacs M;Li X;Schell M;Haura E;Bepler G;Chellappan S
通讯作者：
Chellappan S
影响因子：
11.1
作者：
Bankhead, Armand, III;McMaster, Thomas;Palmbos, Phillip L.
通讯作者：
Palmbos, Phillip L.
影响因子：
64.8
作者：
Ji, Hongbin;Ramsey, Matthew R.;Wong, Kwok-Kin
通讯作者：
Wong, Kwok-Kin
TAp63 通过 miR-133b 抑制结肠癌细胞的转移
影响因子：
8.8
作者：
Lin, C. W.;Li, X. R.;Zhang, Y.;Hu, G.;Guo, Y. H.;Zhou, J. Y.;Du, J.;Lv, L.;Gao, K.;Zhang, Y.;Deng, H.
通讯作者：
Deng, H.