Obesity, metabolism & miscellaneous endocrinology
Prudencio Sáez-Martínez * , Vicente Herrero-Aguayo 1,2,3,4 , Juan M. Jiménez-Vacas 1,2,3,4 , Trinidad Moreno-Montilla 1,2,3,4 , Julia Carrasco-Valiente 1,3,5 , André Sarmento-Cabral 1,2,3,4 , , José López-Miranda 1,3,4,6 , Enrique Gómez-Gómez 1,3,5 , Justo P. Castaño 1,2,3,4 , Manuel D. Gahete 1,2,3,4 & Raúl M. Luque 1,2,3,4
*Maimonides Biomedical Research Institute of Cordoba (IMIBIC); [email protected]; 1Maimonides Institute of Biomedical Research of Cordoba (IMIBIC), 14004 Cordoba, Spain; 2Department of Cell Biology, Physiology and Immunology, University of Cordoba, 14004 Cordoba, Spain3Reina Sofia University Hospital (HURS), 14004 Cordoba, Spain; 4CIBER Physiopathology of Obesity and Nutrition (CIBERobn), 14004 Cordoba, Spain; 5Urology Service, HURS/IMIBIC, 14004 Cordoba, Spain; 6Lipids and Atherosclerosis Unit, Internal Medicine Unit, HURS, 14004 Cordoba, Spain
Background: Prostate cancer (PCa) is one of the most common causes of cancer-related deaths in men worldwide. Early detection of PCa faces severe limitations as PSA displays poor-specificity. Therefore, new diagnostic and therapeutic alternatives are urgently needed.
Objectives: This work was aimed to investigate the miRNA landscape in PCa and explore their putative diagnostic/therapeutic utility.
Methods: 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=380) by qPCR. Additionally, in silico and in vitro assays in normal prostate and PCa cell lines were performed.
Results: The results revealed that the level of 104 miRNAs were significantly altered (p<0.01) in plasma samples from PCa patients compared with controls. Of note, 6 of these miRNAs exhibited a ROC curve capable to perfectly distinguish between control and PCa patients (AUC=1). The validation using an independent cohort demonstrated that miR-107 was the most profoundly altered miRNA in PCa (AUC=0.75). Interestingly, miR-107 outperformed the ability of PSA to distinguish between control and PCa patients, as well as between non-significant (Gleason-Score=6) and significant (Gleason-Score≥7) PCa patients, being its expression correlated with relevant clinical parameters (PSA and testosterone levels, tumor volume). All these comparisons were even stronger in obesity patients (BMI>30). miR-107 levels were also dysregulated in PCa tissues (compared to non-tumor tissues) and in PCa cells (compared to non-tumor cells). Finally, overexpression of miR-107 reduced tumor parameters and altered the expression of FASN/CPT2 (implicated in lipid metabolism) and SRRM1/SRSF2/TIA1 (involved in splicing process) in PCa cells.
Conclusions: Altogether, these results indicate that miR-107 could represent a new diagnostic/therapeutic tool in PCa, especially under obesity condition.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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