Transcriptome of melanoma cell lines resistant to inhibition of the MAPK pathway.

ABSTRACT: Despite major advances in targeted melanoma therapies, drug resistance limits their efficacy. Long noncoding RNAs (lncRNAs) are transcriptome elements that do not encode proteins but are important regulatory molecules. LncRNAs have been implemented in cancer development and response to different therapeutics and are thus potential treatment targets; however, the majority of their functions and molecular interactions remain unexplored. In this study we identify a cytoplasmic intergenic lincRNA (MIRAT), differentially expressed in drug-resistant melanoma samples. MIRAT is upregulated in early drug tolerance to MAPK inhibition and modulates MAPK signaling by binding to the MEK scaffold protein IQGAP1. Collectively, our results present MIRAT’s direct modulatory effect on the MAPK pathway and highlight the relevance of cytoplasmic lncRNA’s as potential targets for drug resistant cancer. RNA-seq data from parental cell lines and their cell clones that are resistant to the MEK inhibitor Trametinib or BRAF inhibitor PLX-4720 (suffix RM; Resistant to MAPK inhibitor)