MicroRNA applications for prostate, ovarian and breast cancer in the era of precision medicine

Abstract

The high degree of conservation in microRNA from Caenorhabditis elegans to humans has enabled relatively rapid implementation of findings in model systems to the clinic. The convergence of the capacity for genomic screening being implemented in the prevailing precision medicine initiative and the capabilities of microRNA to address these changes holds significant promise. However, prostate, ovarian and breast cancers are heterogeneous and face issues of evolving therapeutic resistance. The transforming growth factor-beta (TGFβ) signaling axis plays an important role in the progression of these cancers by regulating microRNAs. Reciprocally, microRNAs regulate TGFβ actions during cancer progression. One must consider the expression of miRNA in the tumor microenvironment a source of biomarkers of disease progression and a viable target for therapeutic targeting. The differential expression pattern of microRNAs in health and disease, therapeutic response and resistance has resulted in its application as robust biomarkers. With two microRNA mimetics in ongoing restorative clinical trials, the paradigm for future clinical studies rests on the current observational trials to validate microRNA markers of disease progression. Some of today’s biomarkers can be translated to the next generation of microRNA-based therapies.

Non-coding RNAs: long non-coding RNAs and microRNAs in endocrine-related cancers

“…There are many recent reviews of the identity, regulation, and targets of miRNAs in BCa, e.g., (Egeland, et al 2015;Klinge 2015;Li, et al 2017c;Muluhngwi and Klinge 2015;O'Bryan, et al 2017;Smith, et al 2017;van Schooneveld, et al 2015;Yahya and Elsayed 2015). miRNAs regulate key pathways dysregulated in BCa including apoptosis, cell cycle, cellular energetics, invasion, metabolism, and metastasis.…”

“…Screening of free and exosomal-associated miRNAs by high throughput sequencing platforms has identified changes in breast, ovarian, and prostate cancers (Smith et al 2017) and in thyroid cancer (Saiselet et al 2016). The release of exosomes containing miRNAs (as well as other ncRNAs, protein, and lipids) and endocytic uptake of the exosomes in recipient cells results in altered regulation of gene translation and has implicated miRNAs as hormones (reviewed in (Bayraktar, et al 2017)).…”

“…However, the miRNA expression profile identified in blood samples depends on the processing of the sample, the miRNA extraction method, contamination, including by lysis of blood cells, and which normalizers are used (Saiselet et al 2016). In addition to the ongoing efforts to standardize exosome and miRNA purification from biological fluids, factors that impact variability in miRNAs detected in circulation include diet, physical activity, and circadian rhythms (reviewed in (Smith et al 2017)). Most of the clinical trials involving mRNAs are observational, i.e., examining circulating in PCa, ovarian and breast cancers to monitor therapeutic responses to chemotherapy or other treatment strategies (reviewed in (Smith et al 2017)).…”

MicroRNAs in breast cancer: Roles, functions, and mechanism of actions

“…TGF-β is also contributes to epithelial-mesenchymal transition (EMT) in breast cancer (Yahya & Elsayed, 2015). TGF-β signaling pathway is capable to control and reciprocally can be controlled by multiple molecules that miRNAs seem to be one of the most noticeable of them (Smith, Agarwal, & Bhowmick, 2017). The miR-200 family frustrates the EMT process by the prevention of TGF-β signaling (Chen, Zhou et al, 2016;Pecot et al, 2013).…”

“…Therefore, miR-191 regulates TGF-β signaling through two direct and indirect mechanisms (Nagpal et al, 2015). Recently, studies found that TGF-β pathway can also modulate miRNAs in breast tumor (Chen, Zhou et al, 2016;Smith et al, 2017). The TGF-β/SMAD4 pathway provokes promoter activity of miR-155, which in turn prompts EMT, invasion, and metastasis through the downregulation of RhoA (Kong et al, 2008).…”