ECE2022 Poster Presentations Diabetes, Obesity, Metabolism and Nutrition (202 abstracts)
Exposing the crosstalk between obesity and prostate cancer: miR-191-5p as personalized diagnostic and therapeutic tool
Francisco Porcel-Pastrana 1,2,3 , Vicente Herrero-Aguayo 1,2,3,4 , Prudencio Sáz-Martínez 1,2,3,4 , Juan M. Jimánez-Vacas 1,2,3,4 , Julia Carrasco-Valiente 3,5,6 , Josá López-Miranda 3,5,7 , Enrique Gómez-Gómez 3,5,6 , Andrá Sarmento-Cabral 1,2,3,4 , Manuel D. Gahete 1,2,3,4 & Raúl M. Luque 1,2,3,4
1University of Cordoba, Department of Cell Biology, Physiology and Immunology, Córdoba, Spain; 2Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), GC27 ‘OncoObesity and Metabolism‘, Córdoba, Spain; 3Reina Sofia University Hospital (HURS), Córdoba, Spain; 4CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Córdoba, Spain; 5Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain; 6Reina Sofia University Hospital (HURS), Urology Service, 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 as well as novel therapeutic targets are urgently needed. As miRNAs have been proposed as promising elements for the identification of novel diagnostic and therapeutic tools for different pathologies, including cancer, we investigated 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. The main changes were validated in an independent cohort (n=295) by quantitative real-time PCR. Additionally, in silico and in vitro assays in normal and tumor prostate cell lines were performed. Results from the array revealed that the expression of 104 miRNAs was significantly altered (P<0.01) in plasma samples from PCa patients compared with 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 validation using an independent cohort of patients 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 stronger in obese patients (BMI > 30). Furthermore, we found that miR-191–5p levels were also dysregulated in PCa cells (compared to non-tumor cells). Moreover, in vitro overexpression of miR-191–5p significantly increased cell proliferation and migration in DU145 and PC-3, two of the most aggressive PCa cell models. Finally, these functional effects were associated with the alteration in key cellular elements that are critical in PCa and obesity pathophysiology. 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.
Fundings: MINECO (PID2019–105564RB-I00/PRE2020–094225/FPU16–06190/FPU17–00263), ISCIII (PI16–00264/PI17–02287), Junta de Andalucía (PI-0094–2020, P20_00442, BIO-0139) and CIBERobn.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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