Long noncoding RNA DNM3OS promotes prostate stromal cells transformation via the miR-29a/29b/COL3A1 and miR-361/TGFß1 axes.
Aging (Albany NY)
; 11(21): 9442-9460, 2019 11 06.
Article
en En
| MEDLINE
| ID: mdl-31694982
ABSTRACT
Transforming growth factor-ß1 (TGFß1)-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 TGFß1 in prostate stromal cells (PrSCs) and might be involved in DNM3OS function in myofibroblasts upon TGFß1 stimulation. Upon TGFß1 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 TGFß1 downstream signaling was similar to that of the TGFß1 inhibitor SB431542. miR-361 could target DNM3OS and TGFß1; DNM3OS competed for miR-361 binding to counteract miR-361-mediated TGFß1 suppression. In conclusion, we identified DNM3OS as a specifically-upregulated lncRNA upon TGFß1 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 TGFß1, thereby promoting TGFß1-induced PrSC transformation into myofibroblasts.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Hiperplasia Prostática
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MicroARNs
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ARN Largo no Codificante
Tipo de estudio:
Prognostic_studies
Límite:
Aged
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Aging (Albany NY)
Asunto de la revista:
GERIATRIA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China