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Regulation of HMGB3 by antitumor miR-205-5p inhibits cancer cell aggressiveness and is involved in prostate cancer pathogenesis
- Source :
- Journal of Human Genetics. 63:195-205
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Our recent determination of a microRNA (miRNA) expression signature in prostate cancer (PCa) revealed that miR-205-5p was significantly reduced in PCa tissues and that it acted as an antitumor miRNA. The aim of this study was to identify oncogenic genes and pathways in PCa cells that were regulated by antitumor miR-205-5p. Genome-wide gene expression analyses and in silico miRNA database searches showed that 37 genes were putative targets of miR-205-5p regulation. Among those genes, elevated expression levels of seven in particular (HMGB3, SPARC, MKI67, CENPF, CDK1, RHOU, and POLR2D) were associated with a shorter disease-free survival in a large number of patients in the The Cancer Genome Atlas (TCGA) database. We focused on high-mobility group box 3 (HMGB3) because it was the most downregulated by ectopic expression of miR-205-5p in PC3 cells and its expression was involved in PCa pathogenesis. Luciferase reporter assays showed that HMGB3 was directly regulated by miR-205-5p in PCa cells. Knockdown studies using si-HMGB3 showed that expression of HMGB3 enhanced PCa cell aggressiveness. Overexpression of HMGB3/HMGB3 was confirmed in naive PCa and castration-resistant PCa (CRPC) clinical specimens. Novel approaches to analysis of antitumor miRNA-regulated RNA networks in PCa cells may provide new insights into the pathogenic mechanisms of the disease.
- Subjects :
- Male
0301 basic medicine
Cell
urologic and male genital diseases
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Cell Line, Tumor
HMGB3 Protein
microRNA
Gene expression
Genetics
medicine
Humans
Genes, Tumor Suppressor
RNA, Neoplasm
Genetics (clinical)
Gene knockdown
biology
CENPF
medicine.disease
Neoplasm Proteins
MicroRNAs
Prostatic Neoplasms, Castration-Resistant
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer cell
biology.protein
Cancer research
Ectopic expression
Subjects
Details
- ISSN :
- 1435232X and 14345161
- Volume :
- 63
- Database :
- OpenAIRE
- Journal :
- Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....2ea8726ffcb31216b7b18d61ac65ff01