Open AccessCritical role of miR-10b in B-RafV600E dependent anchorage independent growth and invasion of melanoma cells
Author(s) -
Ila Datar,
Gardiyawasam Kalpana,
Jungmin Choi,
Tupa Basuroy,
Robert Trumbly,
Sri Krishna Chaitanya Arudra,
Michael McPhee,
Ivana de la Serna,
Kam C. Yeung
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0204387
Subject(s) - biology , mapk/erk pathway , cancer research , melanoma , gene silencing , carcinogenesis , kinase , cell growth , protein kinase a , microbiology and biotechnology , cancer , genetics , gene
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.