miR-124 downregulation leads to breast cancer progression via LncRNA-MALAT1 regulation and CDK4/E2F1 signal activation

Oncotarget. 2016 Mar 29;7(13):16205-16. doi: 10.18632/oncotarget.7578.

Abstract

The long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been recently shown to be dysregulated in several cancers. However, the mechanisms underlying the role of MALAT1 in breast cancer remain unclear. Herein, we showed that MALAT1 was aberrantly increased in breast cancer tissues and cells. MALAT1-siRNA inhibited breast cancer cell proliferation and cell cycle progression in vitro and in vivo. Furthermore, MALAT1 acted as an endogenous potent regulator by directly binding to miR-124 and down-regulating miR-124 expression. In addition, MALAT1 reversed the inhibitory effect of miR-124 on breast cancer proliferation and was involved in the cyclin-dependent kinase 4 (CDK4) expression. Taken together, our data highlight the pivotal role of MALAT1 in breast cancer tumorigenesis. Moreover, the present study elucidated the MALAT1-miR-124-CDK4/E2F1 signaling pathway in breast cancer, which might provide a new approach for tackling breast cancer.

Keywords: MALAT1; breast cancer; cell cycle; cyclin-dependent kinase 4; miR-124.

MeSH terms

  • Animals
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Cyclin-Dependent Kinase 4 / metabolism*
  • Disease Progression
  • Down-Regulation
  • E2F1 Transcription Factor / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Heterografts
  • Humans
  • Kaplan-Meier Estimate
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / metabolism*

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • MALAT1 long non-coding RNA, human
  • MIRN124 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4