miR-34a inhibits melanoma growth by targeting ZEB1

Aging (Albany NY). 2021 Jun 8;13(11):15538-15547. doi: 10.18632/aging.203114. Epub 2021 Jun 8.

Abstract

Melanoma is a highly lethal cutaneous cancer with the tendency for early invasion and metastasis. Integrated miRNA transcriptome sequence analysis of human melanoma tumors and adjacent control tissues identified 17 miRNAs differentially expressed in melanoma tissues: let-7a-5p, let-7b-5p, let-7c, miR-374a-3p, miR-100-5p, miR-7, miR-195, miR-1908, miR-214, miR-221, miR-199a-5p, miR-21, miR-18, miR-34a, miR-199a-3p, miR-92a and miR-106b. Among these, miR-34a was most significantly down-regulated in melanoma tissues, and its expression correlated with TNM melanoma stage. miR-34a overexpression inhibited expression and activity of the transcription factor ZEB1, resulting in decreased proliferation and migration of melanoma cells. Moreover, miR-34a overexpression inhibited ZEB1 expression and melanoma tumor growth in vivo, in a melanoma nude mouse model. Together, these findings demonstrate that miR-34a inhibits melanoma growth by targeting the proto-oncogene ZEB1 and suggest the miR-34a -ZEB1 axis may serve as a novel target for melanoma treatment.

Keywords: ZEB1; melanoma; miR-34a; migration; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Melanoma / genetics
  • Melanoma / pathology*
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / pathology*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • Zinc Finger E-box-Binding Homeobox 1