Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
J Cell Biochem. 2018 Feb;119(2):2189-2199. doi: 10.1002/jcb.26380. Epub 2017 Oct 24.
Breast cancer (BC) is one of the leading causes of cancer deaths worldwide and the most common cancer among women. In our previous study, we revealed that lncRNA TP73-AS1 promotes breast cancer cell proliferation through directly binding to miR-200a. Herein, we evaluated the effect of TP73-AS1 in breast cancer cell invasion and migration, and further demonstrated the direct binding between TP73-AS1 and miR-200a, between miR-200a and 3'UTR of ZEB1, an essential metastasis-related transcription factor. TP73-AS1 promoted ZEB1 expression via competing with ZEB1 3'UTR for miR-200a binding. Moreover, ZEB1 could bind to the promoter region of TP73-AS1 to activate its expression. TP73-AS1 and ZEB1 expression was up-regulated, whereas miR-200a expression was down-regulated in breast cancer tissues. Taken together, we demonstrated a TP73-AS1/miR-200a/ZEB1 regulating loop in breast cancer cells, which promote cancer cell invasion and migration through regulating E-cadherin and Twist expression. Suppressing TP73-AS1 expression to rescue miR-200a expression, thus to inhibit ZEB1 and Twist expression and up-regulate E-cadherin might improve breast cancer cell invasion and migration.
乳腺癌（BC）是全球癌症死亡的主要原因之一，也是女性中最常见的癌症。在我们之前的研究中，我们揭示了长非编码 RNA TP73-AS1 通过直接与 miR-200a 结合来促进乳腺癌细胞增殖。在此，我们评估了 TP73-AS1 在乳腺癌细胞侵袭和迁移中的作用，并进一步证实了 TP73-AS1 与 miR-200a 之间、miR-200a 与作为重要转移相关转录因子的 ZEB1 的 3'UTR 之间的直接结合。TP73-AS1 通过与 ZEB1 3'UTR 竞争与 miR-200a 结合来促进 ZEB1 表达。此外，ZEB1 可以结合到 TP73-AS1 的启动子区域以激活其表达。在乳腺癌组织中，TP73-AS1 和 ZEB1 的表达上调，而 miR-200a 的表达下调。总之，我们在乳腺癌细胞中证实了一个 TP73-AS1/miR-200a/ZEB1 调节环，通过调节 E-钙黏蛋白和 Twist 的表达来促进癌细胞侵袭和迁移。抑制 TP73-AS1 表达以挽救 miR-200a 表达，从而抑制 ZEB1 和 Twist 表达并上调 E-钙黏蛋白可能改善乳腺癌细胞侵袭和迁移。
