Inhibition of RAS-ERK signaling via BRAF downregulation reduces TERT expression of BRAF/NRAS-mutant melanoma cells with TERT promoter mutation. (A) A375, BLM, and UACC257 cells were transduced with shRNA targeting BRAF and analyzed for TERT, BRAF, and uPA expression by qPCR. Plots show relative fold changes in mRNA expression (mean ± SEM) from two experiments. *P < 0.05; **P < 0.01; Student’s t test (two-tailed). (B) Vector and shBRAF-expressing melanoma cells were analyzed for protein levels of BRAF and phosphorylated or total MEK1/2 and ERK1/2. (C) A375 and BLM were transduced with shBRAF, shERK2 alone, or in combination with the TERT WT overexpression construct and analyzed for protein levels of TERT, BRAF, and phosphorylated or total ERK1/2.