ECE2023 Poster Presentations Endocrine-related Cancer (62 abstracts)
MiR-191-5p represents a potential personalized diagnostic and therapeutic tool for PCa patients, especially in obesity conditions
Francisco Porcel-Pastrana 1,2,3,4 , Vicente Herrero-Aguayo 1,2,3,4 , Prudencio Sáez-Martínez 1,2,3,4 , Juan M Jiménez-Vacas 1,2,3,4 , Jesus Perez Gomez 1,2,3,4 , Antonio J. Montero-Hidalgo 1,2,3,4 , Julia Carrasco-Valiente 1,5 , José López-Miranda 3,4,6,7 , Francisco J. Anglada 3,5,6 , Enrique Gómez-Gómez 1,3,5 , André Sarmento-Cabral 1,2,3,4 , Manuel D. Gahete 1,2,3,4 & Raul M. Luque 1,2,3,4
1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), GC27 “OncObesity and metabolism”, Córdoba, Spain; 2University of Cordoba, Department of Cell Biology, Physiology and Immunology, Córdoba, Spain; 3Reina Sofia University Hospital (HURS), Córdoba, Spain; 4CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Córdoba, Spain; 5IMIBIC/HURS, Urology Service, Córdoba, Spain; 6Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; 7HURS, Lipids and Atherosclerosis Unit, Internal Medicine Unit, Córdoba, Spain
Prostate cancer (PCa) is one of the most common causes of cancer-related deaths in men worldwide. Therefore, more specific non-invasive diagnostic biomarkers with potential therapeutic use are urgently needed. As miRNAs have been proposed as promising elements for the identification of novel diagnostic and therapeutic tools for different pathologies, including different cancer types, we investigated herein the miRNA landscape in PCa patients and explored their putative diagnostic/therapeutic utility. Specifically, the miRNome of plasma samples from healthy (n=18) and PCa patients (n=19) was initially determined using an Affymetrix-miRNA array (discovery-cohort). The main changes were validated in an independent and ample validation-cohort [n=202: healthy (n=91) and PCa patients (n=111] by quantitative real-time PCR. Additionally, in silico and in vitro assays in normal (RWPE-1 and PNT-2) and tumor (LNCaP, DU145, and PC-3) prostate cell lines were performed. Results from the discovery-cohort revealed that the expression of 104 miRNAs was significantly altered (P<0.01) in plasma samples from PCa patients vs. healthy controls. Of note, 6 of these miRNAs also exhibited a significant ROC curve to distinguish between healthy and PCa patients with an AUC=1. The analyses in the validation-cohort demonstrated that miR-191-5p was one of the most profoundly altered miRNAs in PCa (P<0.0001) exhibiting an AUC=0.67. Remarkably, miR-191-5p significantly outperformed the ability of prostate-specific antigen (PSA) to distinguish between control and PCa patients, especially in the “grey zone”, which represents the range where PSA levels are less accurate to diagnose PCa. Interestingly, the diagnostic capacity of miR-191-5p was even higher in obese patients (BMI>30). Furthermore, we found that miR-191-5p levels were also dysregulated in PCa cells (vs. non-tumor cells). Moreover, in vitro overexpression of miR-191-5p significantly decreased cell proliferation and migration in LNCaP, DU145, and PC-3 PCa cells line. An in silico approach using diverse bioinformatics tools was performed to discriminate possible targets that may be regulated by miR-191-5p, finding 13 oncogenic targets, which were further explored in response to mimic overexpression. Of all the targets evaluated, TMOD2, a migration-related gene in PCa, was the most consistently decreased, whose levels were also confirmed to be modulated by miR-191-5p. Altogether, our data demonstrate that miR-191-5p might represent a novel and useful personalized diagnostic biomarker in PCa, especially in patients with obesity, as well as a potential therapeutic tool in PCa.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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