Prostate Cancer Secretome and Membrane Proteome from Pten Conditional Knockout Mice Identify Potential Biomarkers for Disease Progression

Autor(es)

Santos, Nilton J. ; Camargo, Ana Carolina Lima ; Carvalho, Hernandes F. ; Justulin, Luis Antonio ; Felisbino, Sergio Luis

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 23, n. 16, p. 26-pg., 2022-08-01.

Resumo

Prostate cancer (PCa) is the second most common cause of mortality among men. Tumor secretome is a promising strategy for understanding the biology of tumor cells and providing markers for disease progression and patient outcomes. Here, transcriptomic-based secretome analysis was performed on the PCa tumor transcriptome of Genetically Engineered Mouse Model (GEMM) Pb-Cre4/Pten(f/f) mice to identify potentially secreted and membrane proteins-PSPs and PMPs. We combined a selection of transcripts from the GSE 94574 dataset and a list of protein-coding genes of the secretome and membrane proteome datasets using the Human Protein Atlas Secretome. Notably, nine deregulated PMPs and PSPs were identified in PCa (DMPK, PLN, KCNQ5, KCNQ4, MYOC, WIF1, BMP7, F3, and MUC1). We verified the gene expression patterns of Differentially Expressed Genes (DEGs) in normal and tumoral human samples using the GEPIA tool. DMPK, KCNQ4, and WIF1 targets were downregulated in PCa samples and in the GSE dataset. A significant association between shorter survival and KCNQ4, PLN, WIF1, and F3 expression was detected in the MSKCC dataset. We further identified six validated miRNAs (mmu-miR-6962-3p, mmu-miR- 6989-3p, mmu-miR-6998-3p, mmu-miR-5627-5p, mmu-miR-15a-3p, and mmu-miR-6922-3p) interactions that target MYOC, KCNQ5, MUC1, and F3. We have characterized the PCa secretome and membrane proteome and have spotted new dysregulated target candidates in PCa. (AU)

• Processo FAPESP: 19/19644-1 - Câncer de próstata: participação das vias da adiponectina e do colágeno tipo X
• Beneficiário: Sérgio Luis Felisbino
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/05952-6 - Metaplasia intestinal no câncer de próstata: incidência e multiplicidade em próstatas de camundongos transgênicos com deleção condicional para o gene PTEN
• Beneficiário: Pedro Pol Ximenes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica