MiRNAs expression in melanoma cells inhibited for RMEL3 and UHMK1.

Abstract

Melanoma is the most aggressive type of skin cancer, specially for its high metastatic potential. U2AF homology motif protein kinase 1 (UHMK1) takes center stage as a key orchestrator of splicing factors, having influence over protein translation. Examination of The Cancer Genome Atlas (TCGA) data showed that tumor samples from cutaneous melanoma patients exhibit higher UHMK1 expression compared to normal tissue. Also, 15% have changes that leads to increased gene expression (unpublished data). UHMK1 was seen to be capable of regulating alternative splicing events of NRAS and MP3K3, which are well-established driver molecules of melanoma development. The lncRNA RMEL3, widely expressed in melanoma, was positively related to UHMK1 expression in melanoma (unpublished data). Both genes are related to the epithelial-mesenchymal transition. Furthermore, analyzes using TCGA data showed regulated miRNAs in samples with high RMEL3 (unpublished data). Three of these miRNAs - miR-200a, miR-200b and miR-944 - are predicted to interact with target sequences in UHMK1 mRNA, indicating possible regulation of UHMK1 expression by these miRNAs. We hypothesize that RMEL3 may regulate UHMK1 expression by sequestering these miRNAs and, therefore, inhibiting their action on UHMK1 mRNA. To test the hypothesis, gene and protein expression of UHMK1 will be evaluated, as well as the levels of the miRNAs, in cells inhibited for RMEL3. The expression of RMEL3 and miRNAs in UHMK1 knockout cells will also be evaluated. Thus, we intend to elucidate the relationship between the RMEL3 and UHMK1 molecules and controlling mechanisms associated with UHMK1 that may be related to the pathways associated with melanogenesis.