MiR-520d-5p directly targets TWIST1 and downregulates the metastamiR miR-10b

Oncotarget. 2014 Dec 15;5(23):12141-50. doi: 10.18632/oncotarget.2559.

Abstract

MicroRNAs are key players in most biological processes. Some microRNAs are involved in the genesis of tumors and are therefore termed oncomiRs, while others, termed metastamiRs, play a significant role in the formation of cancer metastases. Previously, we identified ten different cellular microRNAs that downregulate the expression of MICB, a ligand of the activating NK receptor NKG2D. Interestingly, several of the ten MICB-targeting microRNAs, such as miR-10b, are involved in tumor formation and metastasis. In this work, we identify a complex interplay between these different microRNAs. Specifically, we demonstrate that three of the MICB-targeting microRNAs: miR-20a, miR-17-5p and miR-93, also target the same site in the 3'UTR of TWIST1, a transcription factor implicated in cancer metastasis. Additionally, we show that miR-520d-5p targets a different site in the 3'UTR of TWIST1. We next show that the miR-520d-5p-mediated decrease of TWIST1 expression results in reduced expression of one of its targets, miR-10b, and in the restoration of E-Cadherin expression, which in turn results in reduced cellular motility and invasiveness. Finally, we show that miR-520d-5p leads to reduced proliferation of tumor cells, and that high levels of miR-520d-5p correlate with higher survival rates of cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Blotting, Western
  • Cell Line, Tumor
  • Down-Regulation
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Molecular Sequence Data
  • Neoplasm Invasiveness / genetics*
  • Neoplasms / genetics*
  • Neoplasms / mortality
  • Nuclear Proteins / biosynthesis*
  • Real-Time Polymerase Chain Reaction
  • Twist-Related Protein 1 / biosynthesis*

Substances

  • MIRN10 microRNA, human
  • MIRN520 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • TWIST1 protein, human
  • Twist-Related Protein 1