Cancers, Vol. 13, Pages 4401: Integrated mRNA and miRNA Transcriptomic Analyses Reveals Divergent Mechanisms of Sunitinib Resistance in Clear Cell Renal Cell Carcinoma (ccRCC)
Cancers, Vol. 13, Pages 4401: Integrated mRNA and miRNA Transcriptomic Analyses Reveals Divergent Mechanisms of Sunitinib Resistance in Clear Cell Renal Cell Carcinoma (ccRCC)
Cancers doi: 10.3390/cancers13174401
Authors:
María Armesto
Maitane Marquez
María Arestin
Peio Errarte
Ane Rubio
Lorea Manterola
Jose I. López
Charles H. Lawrie
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 were related to hypoxia/angiogenic pathways, whereas, in Caki-1 cells, they were related to inflammatory/proliferation pathways. The immunotherapy target PD-L1 was consistently up-regulated in resistant cells, and we demonstrated that the silencing of this gene resulted in an increase in sensitivity to sunitinib treatment only in 786-O-resist...
Source: Cancers - Category: Cancer & Oncology Authors: Mar ía Armesto Maitane Marquez Mar ía Arestin Peio Errarte Ane Rubio Lorea Manterola Jose I. L ópez Charles H. Lawrie Tags: Article Source Type: research
More News: Cancer | Cancer & Oncology | Carcinoma | Genetics | Immunotherapy | Kidney Cancer | Legislation | Renal Cell Carcinoma