Critical role of miR-10b in B-RafV600E dependent anchorage independent growth and invasion of melanoma cells

PLoS One. 2019 Apr 17;14(4):e0204387. doi: 10.1371/journal.pone.0204387. eCollection 2019.

Abstract

Recent high-throughput-sequencing of cancer genomes has identified oncogenic mutations in the B-Raf genetic locus as one of the critical events in melanomagenesis. B-Raf encodes a serine/threonine kinase that regulates the MAPK/ERK kinase (MEK) and extracellular signal-regulated kinase (ERK) protein kinase cascade. In normal cells, the activity of B-Raf is tightly regulated and is required for cell growth and survival. B-Raf gain-of-function mutations in melanoma frequently lead to unrestrained growth, enhanced cell invasion and increased viability of cancer cells. Although it is clear that the invasive phenotypes of B-Raf mutated melanoma cells are stringently dependent on B-Raf-MEK-ERK activation, the downstream effector targets that are required for oncogenic B-Raf-mediated melanomagenesis are not well defined. miRNAs have regulatory functions towards the expression of genes that are important in carcinogenesis. We observed that miR-10b expression correlates with the presence of the oncogenic B-Raf (B-RafV600E) mutation in melanoma cells. While expression of miR-10b enhances anchorage-independent growth of B-Raf wild-type melanoma cells, miR-10b silencing decreases B-RafV600E cancer cell invasion in vitro. Importantly, the expression of miR-10b is required for B-RafV600E-mediated anchorage independent growth and invasion of melanoma cells in vitro. Taken together our results suggest that miR-10b is an important mediator of oncogenic B-RafV600E activity in melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Cell Line, Tumor
  • Cell Survival
  • Gain of Function Mutation*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MAP Kinase Signaling System
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Mutation, Missense
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism*
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics

Substances

  • MIRN10 microRNA, human
  • MicroRNAs
  • RNA, Neoplasm
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf

Grant support

UT Foundation, a gift from Clement Lam to KCY, and a Translation Research Stimulation Award (TRSA) from University of Toledo, college of Medicine and Life Sciences supported this work.