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长链非编码RNA TTN-AS1通过调控miR-4677-3p/ZEB1轴驱动肺腺癌细胞的侵袭和迁移。

LncRNA TTN-AS1 drives invasion and migration of lung adenocarcinoma cells via modulation of miR-4677-3p/ZEB1 axis.

作者信息

Zhong Yuanbo, Wang Jin, Lv Wen, Xu Jianzhong, Mei Shanshan, Shan Aijun

机构信息

Emergency Department, Shenzhen People's Hospital, The Second Medical College of Jinan University, Shenzhen, Guangdong, China.

出版信息

J Cell Biochem. 2019 Oct;120(10):17131-17141. doi: 10.1002/jcb.28973. Epub 2019 Jun 7.

Abstract

Lung adenocarcinoma is the most prevalent type of lung cancer with a high incidence and mortality worldwide. Metastasis is the major cause of high death rate in lung cancer and the potential mechanism of lung adenocarcinoma metastasis remains indistinct. Emerging investigations have demonstrated that long noncoding RNA is a kind of non-protein coding RNA and plays a critical role in cancer progression and metastasis. TTN antisense RNA 1 (TTN-AS1) has been reported to promote cell growth and metastasis in cancer. However, the function of TTN-AS1 in lung adenocarcinoma is still to be illustrated. In this study, we observed that TTN-AS1 was upregulated in tissues and cells of lung adenocarcinoma and associated with poor overall survival. TTN-AS1 promoted cell proliferation, migration, invasion, and epithelial-mesenchymal transition in lung cancer. TTN-AS1 directly bound with miR-4677-3p and negatively regulated miR-4677-3p. MiR-4677-3p rescued the inhibitive impacts of TTN-AS1 knockdown on lung adenocarcinoma. Furthermore, zinc finger E-box binding homeobox 1 (ZEB1) was the target of miR-4677-3p, and TTN-AS1 modulated ZEB1 by competing for miR-4677-3p. TTN-AS1 drove the invasion and migration of lung adenocarcinoma cells by targeting the miR-4677-3p/ZEB1 axis. To sum up, our study offers insights into the mechanism of TTN-AS1 in lung adenocarcinoma metastasis and targeting the TTN-AS1/miR-4677-3p/ZEB1 axis may be the potential innovate therapeutic strategy for the patients with lung adenocarcinoma.

摘要

肺腺癌是全球发病率和死亡率都很高的最常见肺癌类型。转移是肺癌高死亡率的主要原因,而肺腺癌转移的潜在机制仍不清楚。新出现的研究表明,长链非编码RNA是一种非蛋白质编码RNA,在癌症进展和转移中起关键作用。据报道,TTN反义RNA 1(TTN-AS1)可促进癌症中的细胞生长和转移。然而,TTN-AS1在肺腺癌中的功能仍有待阐明。在本研究中,我们观察到TTN-AS1在肺腺癌组织和细胞中上调,并与总体生存率低相关。TTN-AS1促进肺癌细胞的增殖、迁移、侵袭和上皮-间质转化。TTN-AS1直接与miR-4677-3p结合并负向调节miR-4677-3p。miR-4677-3p挽救了TTN-AS1敲低对肺腺癌的抑制作用。此外,锌指E盒结合同源框1(ZEB1)是miR-4677-3p的靶标,TTN-AS1通过竞争miR-4677-3p来调节ZEB1。TTN-AS1通过靶向miR-4677-3p/ZEB1轴驱动肺腺癌细胞的侵袭和迁移。总之,我们的研究为TTN-AS1在肺腺癌转移中的机制提供了见解,靶向TTN-AS1/miR-4677-3p/ZEB1轴可能是肺腺癌患者潜在的创新治疗策略。

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