Integrated mRNA and miRNA Transcriptomic Analyses Reveals Divergent Mechanisms of Sunitinib Resistance in Clear Cell Renal Cell Carcinoma (ccRCC).

ABSTRACT: The anti-angiogenic therapy sunitinib remains the standard first-line treatment for meta static clear cell renal cell carcinoma (ccRCC). However, acquired resistance develops in nearly all responsive patients and represents a major source of treatment failure. We used an integrated miRNA and mRNA transcriptomic approach to identify miRNA:target gene interactions involved in sunitinib resistance. Through the generation of stably resistant clones in three ccRCC cell lines (786-O, A498 and Caki-1), we identified non-overlapping miRNA:target gene networks, suggesting divergent mechanisms of sunitinib resistance. Surprisingly, even though the genes involved in these networks were different, they shared targeting by multiple members of the miR-17~92 cluster. In 786-O cells, targeted genes

SUBMITTER: Armesto M 

PROVIDER: S-EPMC8430814 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature