A TP73-AS1/miR-200a/ZEB1 regulating loop promotes breast cancer cell invasion and migration

J Cell Biochem. 2018 Feb;119(2):2189-2199. doi: 10.1002/jcb.26380. Epub 2017 Oct 24.

Abstract

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.

Keywords: TP73-AS1/miR-200a/ZEB1; breast cancer; invasion; migration; regulating loop.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness
  • RNA, Long Noncoding / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / genetics*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • 3' Untranslated Regions
  • MIRN200 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • long non-coding RNA KIAA0495, human