Loss of RBMS1 as a regulatory target of miR-106b influences cell growth, gap closing and colony forming in prostate carcinoma

Abstract

Prostate carcinoma (PCa) is the second most commonly diagnosed cancer in males worldwide. Among hereditary genetic mutations and nutrient factors, a link between the deregulation of microRNA (miRNA) expression and the development of prostate carcinoma is assumed. MiRNAs are small non-coding RNAs which post-transcriptionally regulate gene expression and which are involved in tumour development and progression as oncogenes or tumour suppressors. Although many genes could be confirmed as targets for deregulated miRNAs, the impact of differentially expressed miRNA and their regulatory target genes on prostate tumour development and progression are not fully understood yet. We could validate RBMS1, a barely described RNA-binding protein, as a new target gene for oncogenic miR-106b, which was identified as an induced miRNA in PCa. Further analysis revealed a loss of RBMS1 expression in prostate tumours compared to corresponding normal tissue. Overexpression of RBMS1 in DU145 and LNCaP prostate cancer cells resulted in diminished cell proliferation, colony forming ability as well as in retarded gap closing. Our results demonstrate for the first time a miR-106b dependent downregulation of RBMS1 in prostate carcinoma. Additionally, we show new tumour suppressive properties of RBMS1 whose observed loss may further elucidate the development of PCa.

Construction of miRNA-mRNA network and a nomogram model of prognostic analysis for prostate cancer

“…In this study, hsa-miR-106b-5p, hsa-miR-17-5p and hsa-miR-183-5p were identified to construct a miRNA-mRNA regulatory network of prostate cancer. Hsa-miR-106b-5p, as an oncogene, may down-regulate RBMS1 expression in prostate cancer tissues and affect cell proliferation, gap closure and colony formation (20). Meanwhile, hsa-miR-106b in the blood of prostate cancer patients is significantly higher than that of healthy controls (21).…”

Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer: A Population-Based Case-Control Study and Meta-Analysis

“…The RBMS1 gene is located at chromosome 2q24.2, and it encodes for a protein that binds single stranded DNA/RNA and plays an important role in DNA replication, cell cycle progression, gene transcription, and apoptosis. A recent study demonstrated that the RBMS1 locus acts by regulating the expression of the miR-106b [105], which has been found overexpressed in hepatocellular carcinoma [106], cervical cancer [107], renal carcinoma [108], and gastric cancer [109]. At the same time, Dankert and collaborators have also demostrated that miR-106b can regulate endogenous RBMS1 expression in PCa cell lines and, thereby, act as a tumor suppressor gene with inhibitory effects on colony formation and cell growth [105].…”

“…A recent study demonstrated that the RBMS1 locus acts by regulating the expression of the miR-106b [105], which has been found overexpressed in hepatocellular carcinoma [106], cervical cancer [107], renal carcinoma [108], and gastric cancer [109]. At the same time, Dankert and collaborators have also demostrated that miR-106b can regulate endogenous RBMS1 expression in PCa cell lines and, thereby, act as a tumor suppressor gene with inhibitory effects on colony formation and cell growth [105]. Despite the lack of evidence linking RBMS1 SNPs and risk of PCa, it seems to be plausible to suggest that the presence of genetic variants in the RBMS1 locus might control miR-106b levels and, therefore, favors tumorigenesis.…”

miR-106b as an emerging therapeutic target in cancer

“…Higher expression of miR-106b leads to loss of RBMS1 and influenced the cell growth, colony formation, and gap closing in prostate cancer tissue/cells. 68 …”