MicroRNA-211 Modulates the DUSP6-ERK5 Signaling Axis to Promote BRAF^V600E-Driven Melanoma Growth In Vivo and BRAF/MEK Inhibitor Resistance.

ABSTRACT: MicroRNAs (miRs) are important posttranscriptional regulators of cell fate in both normal and disease states. miR-211 has previously been shown to be a direct regulator of metabolism in BRAF^V600E-mutant melanoma cells in vitro. Here, we report that miR-211 expression promotes the aggressive growth of BRAF^V600E-mutant melanoma xenografts in vivo. miR-211 promoted proliferation through the posttranscriptional activation of extracellular signal-regulated kinase (ERK) 5 signaling, which has recently been implicated in the resistance to BRAF and MAPK/ERK kinase inhibitors. We therefore examined whether miR-211 similarly modulated melanoma resistance to the BRAF inhibitor vemurafenib and the MAPK/ERK kinase inhibitor cobimetinib. Consistent with this model, miR-211 expressi

SUBMITTER: Lee B 

PROVIDER: S-EPMC9004592 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature