MiR-204-5p and miR-211-5p Contribute to BRAF Inhibitor Resistance in Melanoma.

ABSTRACT: Melanoma treatment with the BRAF V600E inhibitor vemurafenib provides therapeutic benefits but the common emergence of drug resistance remains a challenge. We generated A375 melanoma cells resistant to vemurafenib with the goal of investigating changes in miRNA expression patterns that might contribute to resistance. Increased expression of miR-204-5p and miR-211-5p occurring in vemurafenib-resistant cells was determined to impact vemurafenib response. Their expression was rapidly affected by vemurafenib treatment through RNA stabilization. Similar effects were elicited by MEK and ERK inhibitors but not AKT or Rac inhibitors. Ectopic expression of both miRNA in drug-naïve human melanoma cells was sufficient to confer vemurafenib resistance and more robust tumor growth in vivo Conver

SUBMITTER: Diaz-Martinez M 

PROVIDER: S-EPMC5815895 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature