A review of the biological role of miRNAs in prostate cancer suppression and progression

Abstract Background Risk stratification or progression in prostate cancer is performed with the support of clinical-pathological data such as the sum of the Gleason score and serum levels PSA. For several decades, methods aimed at the early detection of prostate cancer have included the determination of PSA serum levels. The aim of this systematic review is to provide an overview about recent advances in the discovery of new molecular biomarkers through transcriptomics, genomics and artificial intelligence that are expected to improve clinical management of the prostate cancer patient. Methods An exhaustive search was conducted by Pubmed, Google Scholar and Connected Papers using keywords relating to the genetics, genomics and artificial intelligence in prostate cancer, it includes “biomarkers”, “non-coding RNAs”, “lncRNAs”, “microRNAs”, “repetitive sequence”, “prognosis”, “prediction”, “whole-genome sequencing”, “RNA-Seq”, “transcriptome”, “machine learning”, and “deep learning”. Results New advances, including the search for changes in novel biomarkers such as mRNAs, microRNAs, lncRNAs, and repetitive sequences, are expected to contribute to an earlier and accurate diagnosis for each patient in the context of precision medicine, thus improving the prognosis and quality of life of patients. We analyze several aspects that are relevant for prostate cancer including its new molecular markers associated with diagnosis, prognosis, and prediction to therapy and how bioinformatic approaches such as machine learning and deep learning can contribute to clinic. Furthermore, we also include current techniques that will allow an earlier diagnosis, such as Spatial Transcriptomics, Exome Sequencing, and Whole-Genome Sequencing. Conclusion Transcriptomic and genomic analysis have contributed to generate knowledge in the field of prostate carcinogenesis, new information about coding and non-coding genes as biomarkers has emerged. Synergies created by the implementation of artificial intelligence to analyze and understand sequencing data have allowed the development of clinical strategies that facilitate decision-making and improve personalized management in prostate cancer. 

/pdf/the-promising-role-of-new-molecular-biomarkers-in-prostate-2ga1bu24.pdf

The promising role of new molecular biomarkers in prostate cancer: from coding and non-coding genes to artificial intelligence approaches

Simple Summary There are diverse reports of the dual role of sirtuin genes and proteins in breast and prostate cancers. This review discusses the current information on the tumor promotion or suppression roles of SIRT1–7 in breast and prostate cancers. Precisely, we highlight that sirtuins regulate various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of both breast and prostate cancer. We also provide evidence of the direct regulation of sirtuins by miRNAs, highlighting the consequences of this regulation in breast and prostate cancer. Overall, this review reveals the potential value of sirtuins as biomarkers and/or targets for improved treatment of breast and prostate cancers. Abstract Mammalian sirtuins (SIRT1–7) are involved in a myriad of cellular processes, including apoptosis, proliferation, differentiation, epithelial-mesenchymal transition, aging, DNA repair, senescence, viability, survival, and stress response. In this review, we discuss the current information on the mechanistic roles of SIRT1–7 and their downstream effects (tumor promotion or suppression) in cancers of the breast and prostate. Specifically, we highlight the involvement of sirtuins in the regulation of various proteins implicated in proliferation, apoptosis, autophagy, chemoresistance, invasion, migration, and metastasis of breast and prostate cancer. Additionally, we highlight the available information regarding SIRT1–7 regulation by miRNAs, laying much emphasis on the consequences in the progression of breast and prostate cancer.

/pdf/the-mechanistic-roles-of-sirtuins-in-breast-and-prostate-24edmlbw.pdf

The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer

Currently used tumor markers for early diagnosis of prostate cancer (PCa) are often lacking sufficient specificity and sensitivity. Therefore, the diagnostic potential of selected microRNAs in comparison to serum PSA levels and PSA density (PSAD) was explored. A panel of 12 PCa-associated microRNAs was quantified by qPCR in urinary sediments from 50 patients with suspected PCa undergoing prostate biopsy, whereupon PCa was detected in 26 patients. Receiver operating characteristic (ROC) curve analyses revealed a potential for non-invasive urine-based PCa detection for miR-16 (AUC = 0.744, p = 0.012; accuracy = 76%) and miR-195 (AUC = 0.729, p = 0.017; accuracy = 70%). While serum PSA showed an insufficient diagnostic value (AUC = 0.564, p = 0.656; accuracy = 50%) in the present cohort, PSAD displayed an adequate diagnostic performance (AUC = 0.708, p = 0.031; accuracy = 70%). Noteworthy, the combination of PSAD with the best candidates miR-16 and miR-195 either individually or simultaneously improved the diagnostic power (AUC = 0.801–0.849, p < 0.05; accuracy = 76–90%). In the sub-group of patients with PSA ≤ 10 ng/mL (n = 34), an inadequate diagnostic power of PSAD alone (AUC = 0.595, p = 0.524; accuracy = 68%) was markedly surpassed by miR-16 and miR-195 individually as well as by their combination with PSAD (AUC = 0.772–0.882, p < 0.05; accuracy = 74–85%). These findings further highlight the potential of urinary microRNAs as molecular markers with high clinical performance. Overall, these results need to be validated in a larger patient cohort.

https://www.mdpi.com/2075-4418/10/8/578/pdf

Evaluation of MicroRNAs as Non-Invasive Diagnostic Markers in Urinary Cells from Patients with Suspected Prostate Cancer

Background: Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Although the prostate-specific antigen (PSA) test is used in clinical practice for screening and/or early detection of PCa, it is not specific, thus resulting in high false-positive rates. MicroRNAs (miRs) provide an opportunity as biomarkers for diagnosis, prognosis, and recurrence of PCa. Because the size of the literature on it is increasing and often controversial, this study aims to consolidate the state-of-art of relevant published research. Methods: A Systematic Literature Review (SLR) approach was applied to analyze a set of 213 scientific publications through a text mining method that makes use of the Latent Dirichlet Allocation (LDA) algorithm. Results and Conclusions: The result of this activity, performed through the MySLR digital platform, allowed us to identify a set of three relevant topics characterizing the investigated research area. We analyzed and discussed all the papers clustered into them. We highlighted that several miRs are associated with PCa progression, and that their detection in patients’ urine seems to be the more reliable and promising non-invasive tool for PCa diagnosis. Finally, we proposed some future research directions to help future scientists advance the field further. 

/pdf/the-potential-of-micrornas-as-non-invasive-prostate-cancer-2gpklw9t.pdf

The Potential of MicroRNAs as Non-Invasive Prostate Cancer Biomarkers: A Systematic Literature Review Based on a Machine Learning Approach

Purpose The microRNAs expression has emerged as a potential biomarker for the diagnosis and prognosis of prostate cancer. This study investigated the expression of miRNA-182 and miRNA-187 in prostate cancer patients and established a correlation between miRNA expression and staging of prostate cancer. Materials and Methods This prospective observational study involved patients undergoing transrectal ultrasound-guided biopsy for suspicion of prostate cancer. Pre-biopsy urine samples and prostatic core tissue samples of the patients were preserved and the miRNA-182 and miRNA-187 were studied. Results Sixty-three patients were included in this study, thirty-three patients were diagnosed with prostate cancer and thirty patients having benign histopathology were considered as controls. The expression of miRNA-182 was significantly increased (p=0.002) and miRNA-187 significantly decreased (p <0.001) in prostate cancer tissue specimens. However, the expression of these miRNAs did not significantly differ in the urine of prostate cancer patients as compared to controls. Serum Prostatic Specific Antigen (PSA) inversely correlated with the median expression of miR-187 in prostatic tissue (p=0.002). Further, the expression of miRNA-187 in prostate cancer tissue was significantly decreased in metastatic prostate cancer (p=0.037). Using ROC analysis, miRNA-187 expression was able to distinguish the presence or absence of bone metastasis [area under ROC (AUROC) (±SD) was 0.873±0.061, p <0.001]. Conclusion The miRNA-182 and miRNA-187 appear to be promising biomarkers in prostate cancer and miRNA-187 can serve as an important diagnostic marker of metastatic prostate cancer.

https://www.scielo.br/pdf/ibju/v46n4/1677-6119-ibju-46-04-0614.pdf

Role of miRNA-182 and miRNA-187 as potential biomarkers in prostate cancer and its correlation with the staging of prostate cancer.

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Role of miRNA-182 and miRNA-187 as potential biomarkers in prostate cancer and its correlation with the staging of prostate cancer.