Fang Jun, Huang Chen, Ke Jing, Li Jia, Zhang Wei, Xue Huimin, Chen Jinpeng
Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
J Cell Biochem. 2020 Dec;121(12):4772-4784. doi: 10.1002/jcb.29700. Epub 2020 Feb 26.
Breast cancer is a common malignant tumor suffered predominantly by women worldwide, which results in serious levels of morbidity and mortality. To control the effects of the cancer, it is critically important to elucidate the pathophysiological processes by which it occurs and develops. Reports have demonstrated that long noncoding RNAs perform a critical role in the development and metastasis of cancers. The lncRNA TTN-AS1 is considered carcinogenic. Nevertheless, the importance and biological functions of TTN-AS1 in breast cancer require greater exploration. In the current paper, we observed that TTN-AS1 expression was significantly upregulated in breast cancer tissues/cells compared with those that are healthy. TTN-AS1 enhanced the proliferation, migration, invasion, and epithelial-mesenchymal transformation of breast cancer cells. Furthermore, a direct target of TTN-AS1, miR-139-5p was negatively regulated. In addition, zinc finger E-box binding homeobox 1 (ZEB1) is an important nuclear transcription factor, the expression of which is increased in multiple tumors. Here, we also found that ZEB1 is a target of miR-139-5p, of which TTN-AS1 could regulate the expression through competition with miR-139-5p. That is, TTN-AS1 promoted proliferation and invasion of breast cancer cells by interaction with the miR-139-5p/ZEB1 axis. In conclusion, the present study aimed to illustrate the significance of TTN-AS1 in breast cancer metastasis and contribute to potentially innovative strategies for its treatment.
乳腺癌是一种常见的恶性肿瘤,全球范围内主要发生在女性身上,会导致严重的发病率和死亡率。为了控制癌症的影响,阐明其发生和发展的病理生理过程至关重要。报告表明,长链非编码RNA在癌症的发生和转移中起着关键作用。lncRNA TTN-AS1被认为具有致癌性。然而,TTN-AS1在乳腺癌中的重要性和生物学功能仍需要进一步探索。在本论文中,我们观察到与健康组织/细胞相比,TTN-AS1在乳腺癌组织/细胞中的表达显著上调。TTN-AS1增强了乳腺癌细胞的增殖、迁移、侵袭和上皮-间质转化。此外,TTN-AS1的直接靶点miR-13 – 5p受到负调控。另外,锌指E盒结合同源框1(ZEB1)是一种重要的核转录因子,其在多种肿瘤中的表达增加。在此,我们还发现ZEB1是miR-139-5p的靶点,TTN-AS1可以通过与miR-139-5p竞争来调节其表达。也就是说,TTN-AS1通过与miR-139-5p/ZEB1轴相互作用促进乳腺癌细胞的增殖和侵袭。总之,本研究旨在阐明TTN-AS1在乳腺癌转移中的意义,并为其治疗提供潜在的创新策略。