An integrated view of the role of miR-130b/301b miRNA cluster in prostate cancer

Abstract

Prostate cancer is a major health problem worldwide due to its high incidence morbidity and mortality. There is currently a need of improved biomarkers, capable to distinguish mild versus aggressive forms of the disease, and thus guide therapeutic decisions. Although miRNAs deregulated in cancer represent exciting candidates as biomarkers, its scientific literature is frequently fragmented in dispersed studies. This problem is aggravated for miRNAs belonging to miRNA gene clusters with shared target genes. The miRNA cluster composed by hsa-mir-130b and hsa-mir-301b precursors was recently involved in prostate cancer pathogenesis, yet different studies assigned it opposite effects on the disease. We sought to elucidate the role of the human miR-130b/301b miRNA cluster in prostate cancer through a comprehensive data analysis of most published clinical cohorts. We interrogated methylomes, transcriptomes and patient clinical data, unifying previous reports and adding original analysis using the largest available cohort (TCGA-PRAD). We found that hsa-miR-130b-3p and hsa-miR-301b-3p are upregulated in neoplastic vs normal prostate tissue, as well as in metastatic vs primary sites. However, this increase in expression is not due to a decrease of the global DNA methylation of the genes in prostate tissues, as the promoter of the gene remains lowly methylated in normal and neoplastic tissue. A comparison of the levels of human miR-130b/301b and all the clinical variables reported for the major available cohorts, yielded positive correlations with malignance, specifically significant for T-stage, residual tumor status and primary therapy outcome. The assessment of the correlations between the hsa-miR-130b-3p and hsa-miR-301b-3p and candidate target genes in clinical samples, supports their repression of tumor suppressor genes in prostate cancer. Altogether, these results favor an oncogenic role of miR-130b/301b cluster in prostate cancer.Electronic supplementary materialThe online version of this article (10.1186/s40164-018-0102-0) contains supplementary material, which is available to authorized users.

Unique, Gender-Dependent Serum microRNA Profile in PLS3 Gene-Related Osteoporosis

“…(29) However, recently it was reported to be linked to bone metabolism in ovariectomized rats, (30) and TargetScan also predicts it to interact directly with several bone-related proteins, such as WNT1, LRP6, and PTEN. Furthermore, miR-301b belongs to the miR-130 gene family together with miR-130b, miR-301a, and miR-130a, (31) which in turn have been reported to partake in osteogenesis and chondrogenesis. (32,33) Last, Liu and colleagues (34) have reported that expression of miR-301b-3p in bone marrow correlates with adipogenic potential of mesenchymal stem cells (MSCs).…”

Adipose Stem Cells and Cancer: Concise Review

“…As described above, miR‐130b packaged in exosomes from prostate cancer cells play a role in ASC‐prostate tumor crosstalk . Additionally, exosomes derived from bone marrow‐derived mesenchymal stem cells promote tumor growth of gastric carcinoma cell line SCG‐7901 .…”

“…Upon priming with PCa conditioned media or PCa derived exosomes, ASCs form prostate‐like neoplastic lesions in vivo and aggressive tumors in secondary recipients . PCa derived exosomes, containing miR‐130b, induce ASC neoplastic reprogramming through upregulation of hRAS and kRAS, and the downregulation of the tumor suppressor gene programmed cell death protein 4 .…”

MiRNA-Based Inspired Approach in Diagnosis of Prostate Cancer

“…The list of miRNAs that are related with prostate cancer is long; for example, Elnaz Pashaei et al conducted a meta-analysis, including 37 microRNAs, of which 15 over expressed and 22 under expressed in prostate cancer [44]. Of these, only the following microRNAs were correlated with prostate cancer: miR-1 [45,46], miR-133b [47], miR-449a [48], miR-137 [49], miR-370 [50], miR-221 [51], miR-449b [35], miR-125a-5p [52], miR-199a-3p [53], miR-301b [38], miR-340 [39], miR-361 [40], miR-363 [54], miR-98 [55]. MiR-1, miR-133B, miR-449B and miR-221 were reported with significant value in prostate cancer prediction after radical prostatectomy.…”

“…MiR-130b/miR-301b cluster was found to be up-regulated in prostate cancer. Their oncogenic role was determined by a complex analysis of patient cohort samples correlated with gene expression data [38]. Moreover, miR-301b-3p is an important target since hypoxia, a very common phenomenon [87], will enhance its expression level in prostate cancer [88].…”