BRAFV600E remodels the melanocyte transcriptome and induces BANCR to regulate melanoma cell migration

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• Cancer genomics primarily focuses on protein-coding genes, leaving the role of oncogenes in regulating non-coding RNA expression largely unexplored.
• The BRAF oncogene, particularly the V600E mutation, is highly prevalent in melanoma, driving tumor development.
• Understanding oncogene-driven transcriptome alterations is crucial for identifying novel cancer biomarkers and therapeutic targets.

Purpose of the Study:

• To investigate the impact of the BRAF(V600E) oncogene on the melanocyte transcriptome, including both protein-coding and non-coding RNAs.
• To identify novel, potentially oncogene-regulated transcripts in melanoma.
• To explore the functional significance of identified transcripts in melanoma progression.

Main Methods:

• RNA sequencing (RNA-seq) was performed on normal human melanocytes with and without BRAF(V600E) expression.
• RNA-seq was also conducted on BRAF(V600E)-mutant human melanoma tissues to validate findings in a disease context.
• Bioinformatic analyses were used to identify differentially expressed transcripts, assess coding potential, and analyze regulatory elements.

Main Results:

• BRAF(V600E) significantly altered the expression of 1027 protein-coding transcripts and 39 annotated long noncoding RNAs (lncRNAs).
• Seventy unannotated, potentially novel intergenic transcripts were identified, with coding potential analysis suggesting they are likely new lncRNAs.
• A novel BRAF-regulated lncRNA, BANCR, was identified and found to be overexpressed in melanoma, playing a role in cell migration, which could be modulated by CXCL11.

Conclusions:

• Oncogenic BRAF profoundly impacts the melanocyte transcriptome, regulating both coding and non-coding RNA expression.
• The study identified novel lncRNAs, including BANCR, with potential roles in melanoma pathogenesis and clinical relevance.
• Combining RNA-seq from normal cells and matched cancers is an effective strategy for discovering oncogene-regulated transcripts with clinical significance.