miR-221/222 promote tumor growth and suppress apoptosis by targeting lncRNA GAS5 in breast cancer

Biosci Rep. 2019 Jan 15;39(1):BSR20181859. doi: 10.1042/BSR20181859. Print 2019 Jan 31.

Abstract

MicroRNAs (miRNAs) are 21-23-nucleotide, short, non-coding RNAs that play important roles in virtually all biological pathways in mammals and other multicellular organisms. The association of miR-221 and miR-222 (miR-221/222) for breast cancer is critical, but their detailed roles in its development and progression remain unclear. In the present study, we found that miR-221/222 were consistently up-regulated in breast cancer tissues. We then investigated the molecular mechanisms by which miR-221/222 contributed to breast cancer and identified growth arrest-specific transcript 5 (GAS5) as a direct target gene of miR-221/222. In contrast with the up-regulated expression levels of miR-221/222, GAS5 levels were significantly down-regulated and negatively correlated with miR-221/222 in breast cancer tissues. In addition, we showed that miR-221/222 inhibitors increased cellular apoptosis, miR-221/222 mimics decreased the cell apoptosis in breast cancer cells, and restoration of GAS5 expression attenuated the anti-apoptotic effects of miR-221/222 in breast cancer cells, indicating that GAS5 was a direct mediator of miR-221/222 function. Finally, we showed that miR-221/222 suppressed GAS5 expression significantly and enhanced tumor growth in a mouse model of breast cancer xenografts. The present study highlighted the important role of miR-221/222 as oncomiRs in breast cancer, which inhibited GAS5 translation. These findings may provide a new perspective for the molecular mechanism of breast carcinogenesis and provide a novel approach to the treatment of breast cancer.

Keywords: GAS5; apoptosis; breast cancer; miR-221/222.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Antagomirs / genetics
  • Antagomirs / metabolism
  • Apoptosis / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors / chemistry
  • Genetic Vectors / metabolism
  • Humans
  • Lentivirus / genetics
  • Lentivirus / metabolism
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antagomirs
  • GAS5 long non-coding RNA, human
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering