miRNAs as drivers of TMPRSS2-ERG negative prostate tumors in African American men

Abstract

African Americans (AAs) who have PCa typically have more aggressive disease and make up a disproportionate number of the disease deaths, relative to European Americans (EAs). TMPRSS2 translocations, a common event in EA patients, are exploited in diagnostic and prognostic settings, whereas they are diminished in frequency in AA men. Thus, these patients with TMPRSS2 fusion-negative disease represent an under-investigated patient group. We propose that epigenetic events are a significant and alternative driver of aggressive disease in fusion-negative PCa. To reveal epigenetically governed microRNAs (miRNAs) that are enriched in fusion-negative disease and associated with aggressive in AA PCa, we leveraged both our experimental evidence and publically available data. These analyses identified 18 miRNAs that are differentially altered in fusion-negative disease, associated with DNA CpG methylation, and implicated in aggressive and AA PCas. Understanding the relationships between miRNA expression, upstream epigenetic regulation by DNA methylation, and downstream regulation of mRNA targets in fusion negative disease is imperative to understanding the biological basis of the racial health disparity in PCa.

Diagnostic and prognostic value of microRNA-628 for cancers

“…Recently, due to their roles in tumorigenesis and their correlation with clinical characteristics, miRNAs have attracted wide attention. Further, accumulating evidence supports that their abnormal expression levels are associated with various diseases, such as lung cancer 47 , 48 , prostate cancer 22 , 49 , 50 , and cervical cancer 51 , 52 . More importantly, miRNAs present in various biological materials, like serum, plasma, and tissue, are extremely stable, even in extreme thermal environment 53 , 54 .…”

Altered expression of miRNAs and mRNAs reveals the potential regulatory role of miRNAs in the developmental process of early weaned goats

“…Biological process functional analysis indicated that ASB14 may be associated with heart failure through the regulation of protein ubiquitination, which requires experimental validation [39]. TMPRSS2 functions in prostate carcinogenesis [40] and contributes to the spread of several viruses [41]. High levels of MMP-2 are associated with tumor progression, including cancer cell proliferation, invasion, metastasis, and progression [42,43].…”

Epigenetic basis of cancer health disparities: Looking beyond genetic differences

“…Such down-regulation of miR-212 correlated with aberrant expression of hnRNP H1, as well as the androgen receptor, resulting in castration-resistance. In a more recent article that focused on TMPRSS2 (transmembrane protease, serine-2) translocations, a panel of 18 differentially altered miRNAs was identified [136]. These miRNAs were associated with DNA CpG methylation, and the resulting aggressive disease in TMPRSS2 fusion-negative prostate cancers.…”

“…These miRNAs were associated with DNA CpG methylation, and the resulting aggressive disease in TMPRSS2 fusion-negative prostate cancers. Among these, miR-125b, miR-17, miR-29 and miR-200b have been studied in prostate cancer [136]. miR-125b has been demonstrated to facilitate the development of castration-resistant prostate cancer by targeting the repressor of AR signaling, NCOR2/SMRT (nuclear receptor corepressor 2/silencing mediator of retinoic acid and thyroid hormone receptor) [137].…”