Impaired expression of serine/arginine protein kinase 2 (SRPK2) affects melanoma progression.

Autor:	Caetano MMM; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Moreira GA; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., da Silva MR; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Guimarães GR; Laboratório de Bioinformática e Biologia Computacional, Divisão de Pesquisa Experimental e Translacional, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., Santos LO; Laboratório de Bioinformática e Biologia Computacional, Divisão de Pesquisa Experimental e Translacional, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., Pacheco AA; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Siqueira RP; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Mendes FC; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Marques Da Silva EA; Departamento de Biologia Geral, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Junior AS; Departamento de Veterinária, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Rangel Fietto JL; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil., Saito Â; Laboratório Nacional de Biociências (LNBio), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), Campinas, Brazil., Boroni M; Laboratório de Bioinformática e Biologia Computacional, Divisão de Pesquisa Experimental e Translacional, Instituto Nacional de Câncer (INCA), Rio de Janeiro, Brazil., Bressan GC; Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa (UFV), Viçosa, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2022 Sep 23; Vol. 13, pp. 979735. Date of Electronic Publication: 2022 Sep 23 (Print Publication: 2022).
DOI:	10.3389/fgene.2022.979735
Abstrakt:	Melanoma is one of the most aggressive tumors, and its lethality is associated with the ability of malignant cells to migrate and invade surrounding tissues to colonize distant organs and to generate widespread metastasis. The serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2) are classically related to the control of pre-mRNA splicing through SR protein phosphorylation and have been found overexpressed in many types of cancer, including melanoma. Previously, we have demonstrated that the pharmacological inhibition of SRPKs impairs pulmonary colonization of metastatic melanoma in mice. As the used compounds could target at least both SRPK1 and SRPK2, here we sought to obtain additional clues regarding the involvement of these paralogs in melanoma progression. We analyzed single-cell RNA sequencing data of melanoma patient cohorts and found that SRPK2 expression in melanoma cells is associated with poor prognosis. Consistently, CRISPR-Cas9 genome targeting of SRPK2, but not SRPK1, impaired actin polymerization dynamics as well as the proliferative and invasive capacity of B16F10 cells in vitro . In further in vivo experiments, genetic targeting of SRPK2, but not SRPK1, reduced tumor progression in both subcutaneous and caudal vein melanoma induction models. Taken together, these findings suggest different functional roles for SRPK1/2 in metastatic melanoma and highlight the relevance of pursuing selective pharmacological inhibitors of SRPK2. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Caetano, Moreira, Silva, Guimarães, Santos, Pacheco, Siqueira, Mendes, Marques Da Silva, Junior, Rangel Fietto, Saito, Boroni and Bressan.)
Databáze:	MEDLINE
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