Long noncoding RNA DNM3OS promotes prostate stromal cells transformation via the miR-29a/29b/COL3A1 and miR-361/TGF?1 axes.

ABSTRACT: Transforming growth factor-?1 (TGF?1)-induced differentiation into and the activation of myofibroblasts have been regarded as critical events in benign prostatic hyperplasia (BPH); however, the underlying mechanisms of BPH pathogenesis remain unclear. Microarray profiling, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation, and Gene Ontology (GO) enrichment analysis were performed to confirm the candidate genes and long non-coding RNA (lncRNAs) related to BPH. Collagen Type III (COL3A1) was significantly upregulated by TGF?1 in prostate stromal cells (PrSCs) and might be involved in DNM3OS function in myofibroblasts upon TGF?1 stimulation. Upon TGF?1 stimulation, COL3A1 protein was decreased by DNM3OS silencing. miR-29a and miR-29b could directly bind to the DNM3OS and COL3A1 3' untranslated region (UTR)s to negatively regulate their expression, and by serving as a competing endogenous RNAs (ceRNA), DNM3OS competed with COL3A1 for miR-29a/29b binding, therefore counteracting miR-29a/29b-mediated COL3A1 suppression. The effect of DNM3OS silencing on ECM components and TGF?1 downstream signaling was similar to that of the TGF?1 inhibitor SB431542. miR-361 could target DNM3OS and TGF?1; DNM3OS competed for miR-361 binding to counteract miR-361-mediated TGF?1 suppression. In conclusion, we identified DNM3OS as a specifically-upregulated lncRNA upon TGF?1 stimulation in PrSCs; by serving as a ceRNA for the miR-29a/29b cluster and miR-361, DNM3OS eliminated miRNA-mediated suppression of COL3A1 and TGF?1, thereby promoting TGF?1-induced PrSC transformation into myofibroblasts.

SUBMITTER: Wang R 

PROVIDER: S-EPMC6874426 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature