Critical role of miR-10b in B-RafV600E dependent anchorage independent growth and invasion of melanoma cells.
Amino Acid Substitution
Cell Line, Tumor
Cell Survival
Gain of Function Mutation
Gene Expression Regulation, Neoplastic
Humans
MAP Kinase Signaling System
Melanoma
/ genetics
MicroRNAs
/ biosynthesis
Mutation, Missense
Neoplasm Invasiveness
Proto-Oncogene Proteins B-raf
/ genetics
RNA, Neoplasm
/ biosynthesis
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
05
09
2018
accepted:
19
03
2019
entrez:
18
4
2019
pubmed:
18
4
2019
medline:
18
12
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30995246
doi: 10.1371/journal.pone.0204387
pii: PONE-D-18-26080
pmc: PMC6469749
doi:
Substances chimiques
MIRN10 microRNA, human
0
MicroRNAs
0
RNA, Neoplasm
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0204387Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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