Critical role of miR-10b in B-Raf V600E dependent anchorage independent growth and invasion of melanoma cells

Ila Datar, Gardiyawasam Kalpana, Jungmin Choi, Tupa Basuroy, Robert Trumbly, Sri Krishna Chaitanya Arudra, Michael D. McPhee, Ivana De La Serna, Kam C. Yeung

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

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-Raf V600E ) 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-Raf V600E cancer cell invasion in vitro. Importantly, the expression of miR-10b is required for B-Raf V600E -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-Raf V600E activity in melanoma.

Original languageEnglish
Article numbere0204387
JournalPloS one
Volume14
Issue number4
DOIs
Publication statusPublished - 2019 Apr
Externally publishedYes

ASJC Scopus subject areas

  • General

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