Systematic review and meta-analysis of the prognostic significance of microRNAs related to metastatic and EMT process among prostate cancer patients

Abstract

The ability of tumor cells to spread from their origin place and form secondary tumor foci is determined by the epithelial–mesenchymal transition process. In epithelial tumors such as prostate cancer (PCa), the loss of intercellular interactions can be observed as a change in expression of polarity proteins. Epithelial cells acquire ability to migrate, what leads to the formation of distal metastases. In recent years, the interest in miRNA molecules as potential future treatment options has increased. In tumor microenvironment, miRNAs have the ability to regulate signal transduction pathways, where they can act as suppressors or oncogenes. MiRNAs are secreted by cancer cells, and the changes in their expression levels are closely related to a cancer progression, including epithelial–mesenchymal transition. These molecules offer new diagnostic and therapeutic possibilities. Therapeutics which make use of synthesized RNA fragments and mimic or block miRNAs affected in PCa, may lead to inhibition of tumor progression and even disease re-emission. Based on appropriate qualification criteria, we conducted a selection process to identify scientific articles describing miRNAs and their relation to epithelial–mesenchymal transition in PCa patients. The studies were published in English on Pubmed, Scopus and the Web of Science before August 08, 2019. Hazard ratios (HRs) and 95% confidence intervals (CI) as well as total Gleason score were used to assess the concordance between miRNAs and presence of metastases. A total of 13 studies were included in our meta-analysis, representing 1608 PCa patients and 15 miRNA molecules. Our study clarifies a relationship between the clinicopathological features of PCa and the aberrant expression of several miRNA as well as the complex mechanism of miRNA molecules involvement in the induction and promotion of the metastatic mechanism in PCa.

Prognostic value of miR-21 for prostate cancer: a systematic review and meta-analysis

“…It is worth remembering however that miRNAs often work synergistically as a regulatory network for gene expression, so the involvement of miR-21 with other miRNAs should be considered. For instance, while this paper was being prepared, another systematic review and meta-analysis was published which reported the prognostic significance of 15 microRNAs related to metastasis and EMT process in PCa patients [ 105 ]. Surprisingly, miR-21 was not included among them, but the authors did acknowledge the link between their selected miRNAs and miR-21 in their discussion, and they concluded that a miRNA panel of biomarkers would be optimal to determine progression risk.…”

Role of Metastasis-Related microRNAs in Prostate Cancer Progression and Treatment

“…The miRNA-34 family comprises miR-34a, miR-34b, and miR-34c. miR-34a is located on chromosome 1p36, whereas, in the human genome, miR-34b and miR-34c are located on chromosome 11q23, clustered as homologous genes that share a common primary transcript [54]. The miR-34 family members are regarded as tumor-suppressive miRNAs due to their synergistic effect with the tumor suppressor p53, as well as their involvement in EMT via EMT-TFs.…”

“…miR-34a inhibits metastasis by directly repressing CD44 [87], a cancer stem cell marker that has been considered to indicate a more mesenchymal phenotype of human PCa cells [88]. Moreover, miR-34a represses WNT/β-catenin, JAK/STAT3, and PI3K/AKT signaling, all of which have been related to PCa progression [54,86,87]. miR-34a also down-regulates the oncoprotein STMN1 through the CtBP1\miR-34a\STMN1\GDF15 axis and prevents PCa progression in vivo [89].…”

“…miR-34a also down-regulates the oncoprotein STMN1 through the CtBP1\miR-34a\STMN1\GDF15 axis and prevents PCa progression in vivo [89]. MiR-34b similarly carries out its migrationand invasion-inhibiting role by regulating the TGF-β pathway via phosphorylation of SMAD3 (TGF-β/SMAD3 pathway) in metastatic PCa [54]. In a recent study from our group, miR-34 is also included in a metastasis-related interaction network of PCa, in which miR-34 expression is down-regulated with increasing metastatic potential of spontaneous metastasis xenograft models.…”

The Role of miRNAs in the Regulation of Endometrial Cancer Invasiveness and Metastasis—A Systematic Review

“…Despite the identification of many prognostic biomarkers in EC [235,236], none of them are routinely used for diagnostic or prognostic purposes. Recent systematic reviews and meta-analyses revealed the clinical utility for the use of miRNAs as biomarkers in a variety of cancer, including bladder cancer [237], prostate cancer [238], ovarian cancer [239], and breast cancer [240], which makes miRNAs promising candidate for biomarkers in EC (Figure 5). Importantly, dysregulation of miRNAs expression can be also detected in plasma or serum (Figure 5).…”