Dataset Information

CTBP1 depletion on prostate tumors deregulates miRNA/mRNA expression and impairs cancer progression in metabolic syndrome mice.

ABSTRACT: About 20% of prostate cancer (PCa) patients progress to metastatic disease. Metabolic syndrome (MeS) is a pathophysiological disorder that increases PCa risk and aggressiveness. C-terminal binding protein (CTBP1) is a transcriptional corepressor that is activated by high-fat diet (HFD). Previously, our group established a MeS/PCa mice model that identified CTBP1 as a novel link associating both diseases. Here, we integrated in vitro (prostate tumor cell lines) and in vivo (MeS/PCa NSG mice) models with molecular and cell biology techniques to investigate MeS/CTBP1 impact over PCa progression, particularly over cell adhesion, mRNA/miRNA expression and PCa spontaneous metastasis development. We found that CTBP1/MeS regulated expression of genes relevant to cell adhesion and PCa progression, such as cadherins, integrins, connexins, and miRNAs in PC3 xenografts. CTBP1 diminished PCa cell adhesion, membrane attachment to substrate and increased filopodia number by modulating gene expression to favor a mesenchymal phenotype. NSG mice fed with HFD and inoculated with CTBP1-depleted PC3 cells, showed a decreased number and size of lung metastases compared to control. Finally, CTBP1 and HFD reduce hsa-mir-30b-5p plasma levels in mice. This study uncovers for the first time the role of CTBP1/MeS in PCa progression and its molecular targets.

SUBMITTER: Dalton GN

PROVIDER: S-EPMC6443782 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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CTBP1 depletion on prostate tumors deregulates miRNA/mRNA expression and impairs cancer progression in metabolic syndrome mice.

Dalton Guillermo Nicolás GN Massillo Cintia C Scalise Georgina Daniela GD Duca Rocío R Porretti Juliana J Farré Paula Lucia PL Gardner Kevin K Paez Alejandra A Gueron Geraldine G De Luca Paola P De Siervi Adriana A

Cell death & disease 20190401 4

About 20% of prostate cancer (PCa) patients progress to metastatic disease. Metabolic syndrome (MeS) is a pathophysiological disorder that increases PCa risk and aggressiveness. C-terminal binding protein (CTBP1) is a transcriptional corepressor that is activated by high-fat diet (HFD). Previously, our group established a MeS/PCa mice model that identified CTBP1 as a novel link associating both diseases. Here, we integrated in vitro (prostate tumor cell lines) and in vivo (MeS/PCa NSG mice) mode ...[more]

PMID: 30931931

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Project description:Prostate cancer (PC) is one of the major male cancers. Differential diagnosis of PC is indispensable for the individual therapy, i.e., Gleason score (GS) that describes the grade of cancer can be used to choose the appropriate therapy. However, the current techniques for PC diagnosis and prognosis are not always effective. To identify potential markers that could be used for differential diagnosis of PC, we analyzed miRNA-mRNA interactions and we build specific networks for PC onset and progression. Key differentially expressed miRNAs for each GS were selected by calculating three parameters of network topology measures: the number of their single regulated mRNAs (NSR), the number of target genes (NTG) and NSR/NTG. miRNAs that obtained a high statistically significant value of these three parameters were chosen as potential biomarkers for computational validation and pathway analysis. 20 miRNAs were identified as key candidates for PC. 8 out of 20 miRNAs (miR-25-3p, miR-93-3p, miR-122-5p, miR-183-5p, miR-615-3p, miR-7-5p, miR-375, and miR-92a-3p) were differentially expressed in all GS and proposed as biomarkers for PC onset. In addition, "Extracellular-receptor interaction", "Focal adhesion", and "microRNAs in cancer" were significantly enriched by the differentially expressed target genes of the identified miRNAs. miR-10a-5p was found to be differentially expressed in GS 6, 7, and 8 in PC samples. 3 miRNAs were identified as PC GS-specific differentially expressed miRNAs: miR-155-5p was identified in PC samples with GS 6, and miR-142-3p and miR-296-3p in PC samples with GS 9. The efficacy of 20 miRNAs as potential biomarkers was revealed with a Random Forest classification using an independent dataset. The results demonstrated our 20 miRNAs achieved a better performance (AUC: 0.73) than miRNAs selected with Boruta algorithm (AUC: 0.55), a method for the automated feature extraction. Studying miRNA-mRNA associations, key miRNAs were identified with a computational approach for PC onset and progression. Further experimental validations are needed for future translational development.

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Dataset Information

CTBP1 depletion on prostate tumors deregulates miRNA/mRNA expression and impairs cancer progression in metabolic syndrome mice.

Publications

CTBP1 depletion on prostate tumors deregulates miRNA/mRNA expression and impairs cancer progression in metabolic syndrome mice.

Similar Datasets

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