miR-192, miR-194, miR-215, miR-200c and miR-141 are downregulated and their common target ACVR2B is strongly expressed in renal childhood neoplasms

Abstract

Micro RNAs (miRNAs) play an important role during renal development and show a tissue-specific enrichment in the kidney. Nephroblastomas, embryonal renal neoplasms of childhood, are considered to develop from nephrogenic rests (NRs) and resemble morphologically and genetically developing kidney. We therefore investigated the role of kidney-enriched miRNAs in the pathogenesis of nephroblastomas. miR-192, miR-215 and miR-194 had a significantly lower expression in nephroblastomas regardless of the subtype compared with mature kidney measured by quantitative real-time-PCR. miR-141 and miR-200c showed a significantly lower expression in blastema-type and mixed-type tumors. In comparison with NRs, a significantly lower expression of miR-192, miR-194 and miR-215 was identified in blastema-type, mixed-type and stroma-type nephroblastomas and of miR-141 and miR-200c in blastema-type tumors. Kidney parenchyma had a significantly higher expression of miR-192, miR-194, miR-215 and miR-200c compared with NRs. In this study, the activin receptor type 2B (ACVR2B), a member of the transforming growth factor (TGF)-β pathway, was identified as single common target gene for miR-192, miR-215, miR-194, miR-141 and miR-200c in silico for the first time. The interaction between all five miRNAs and ACVR2B was also verified by an in vitro assay. Additionally, a distinct protein expression of ACVR2B was detected in 53 of 55 nephroblastomas paralleled by an upregulation of ACVR2B messenger RNA demonstrated in 25 nephroblastomas of all subtypes. A differential regulation of ACVR2B by miRNAs in NRs and nephroblastomas appears to be an important step in the pathogenesis of nephroblastomas implicating for the first time the TGF-β pathway in this process.

Demethylation drug 5-Aza-2′-deoxycytidine-induced upregulation of miR-200c inhibits the migration, invasion and epithelial-mesenchymal transition of clear cell renal cell carcinoma in vitro

“…In addition, Senanayake et al (20) identified that miR-200c was downregulated and its target Activin A Receptor, Type IIB was markedly expressed in renal childhood neoplasms (20). In the present study, it was additionally demonstrated that miR-200c was DNA methylation in the CpG island of the gene promoter is the most frequent epigenetic modification in eukaryotic genomes, and hypermethylation typically inhibits gene transcription (21).…”

“…MicroRNAs (miRs) are a type of small non-coding RNA (19)(20)(21)(22)(23)(24)(25) nucleotides) that possess prominent roles in the regulation of genes (6). MiRs typically inhibit gene expression by directly binding the 3'-untranslated region of their target messenger (m)RNAs, causing repression of translation or mRNA degradation (7).…”

MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancer

“…With regard to miR-215, several targets have been confirmed in previous studies including protein tyrosine phosphatase receptor type T (PTPRT) , thymidylate synthase (TS) (Song et al, 2010), dihydrofolate reductase (DHFR) (Song et al, 2010), retinoblastoma tumor suppressor gene 1 (RB1) (Deng et al, 2014), activated leukocyte cell adhesion molecule (ALCAM) (Jin et al, 2011), and activin receptor type 2B (ACVR2B) (Senanayake et al, 2012). ZEB2, as a tumor-promoting gene, has been found to be upregulated in different tumor types, and identified as a target gene of a number of miRs.…”

MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1

“…The miR-200 family was involved in the process of mesenchymal-epithelial transition (MET) during renal development [13]. A recent study found that miR-200c was dramatically decreased in clear cell renal carcinomas compared with non-malignant samples [14]. It was showed that restoration of mature miR-200c in renal cell carcinoma markedly inhibited cancer cell proliferation, suggesting that miR-200c might be a candidate tumor suppressor.…”