MicroRNA-3151 inactivates TP53 in BRAF -mutated human malignancies

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Abstract
Significance: Activating mutations in the B-Raf proto-oncogene serine/threonine kinase ( BRAF ) gene occur in many tumor types, the highest incidence being in malignant melanoma and papillary thyroid carcinoma. In patients with BRAF mutations tumor progression is more rapid than in patients without these mutations. Therapeutic strategies presently aim at inhibiting BRAF resulting in slower tumor progression; however, lasting remission is rarely accomplished. In this paper we identify the oncomiR-3151 as a downstream effector of mutated BRAF. MicroRNA-3151 (miR-3151) targets TP53 and other members of the TP53 pathway resulting in its inhibition. Simultaneous inhibition of BRAF and miR-3151 potentiates the effects on tumor cell growth. These data establish a link between mutated BRAF and the TP53 pathway, allowing novel therapeutic approaches to be considered.
Funding Information
  • HHS | NIH | National Cancer Institute (CA16058)
  • HHS | NIH | National Cancer Institute (CA124570)

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