Pd38-06 Risk Score Prediction Model for Bladder Cancer Using Combination of Immunoscore and Pathological Staging
Year: 2016
Type: article
Abstract: now.The development of the new treatment regimens based on the current genomics approach is required for BC.Our recent study of microRNA (miRNA) expression signature by deep sequencing revealed that miR-145-5p and miR-145-3p were significantly reduced in BC tissues compared with normal bladder epithelium.In miRNA biogenesis, during RISC loading one strand (passenger strand) of miRNA duplex is discarded, while the other strand (guide strand) is retained to direct recruitment of the RISC to target mRNAs.Our deep sequencing data suggested that both strands of pre-miRNA-145, miR-145-5p and miR-145-3p act as tumor-suppressors in BC cells.The aim of the present study was to investigate the functional significance of miR-145-5p and miR-145-3p in BC cells and to identify these miRNAs mediated target genes involved in BC oncogenesis and metastasis.METHODS: Expression levels of miR-145-5p/3p and its target gene in clinical tissues (71 BCs and 12 normal bladder epithelia) and cell lines ( T24 and BOY ) were evaluated by qRT-PCR.The functional studies of these miRNAs and the target genes were performed by cell proliferation, migration, invasion, and apoptosis assays in BC cell lines.Genome-wide gene expression analysis and in silico analysis using microRNA.organd GEO database, were applied to investigate molecular target regulated by these miRNAs.A luciferase reporter assay was carried out to determine whether 3' UTR of target gene have actual biding sites for these miRNAs.RESULTS: The expression levels of miR-145-5p/3p were significantly reduced in BC tissues and the cell lines (p<0.0001).Restoration of these miRNAs revealed that both miRNAs significantly induced apoptosis and inhibited proliferation, migration, and invasion (p<0.0001).Ubiquitin-like, containing PHD and RING finger domains 1 (UHRF1) was identified as a direct target gene of miR-145-5p/3p by luciferase reporter assays.CONCLUSIONS: Two mature miRNAs, miR-145-5p and miR-145-3p derived from pre-miR-145 act as tumor-suppressors in BC cells.UHRF1 expression was regulated by miR-145-5p and miR-145-3p in BC cells, and aberrant expression of UHRF1 might be enhanced BC metastasis.Identification of novel target gene regulated by dual tumorsuppressors miR-145-5p and miR-145p-3p may lead to a better understanding of BC and the development of new therapeutic strategies to treat this disease.
Source: The Journal of Urology
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2335642203