Dataset Information

ADAR2/miR-589-3p axis controls glioblastoma cell migration/invasion.

ABSTRACT: Recent studies have reported the emerging role of microRNAs (miRNAs) in human cancers. We systematically characterized miRNA expression and editing in the human brain, which displays the highest number of A-to-I RNA editing sites among human tissues, and in de novo glioblastoma brain cancer. We identified 299 miRNAs altered in their expression and 24 miRNAs differently edited in human brain compared to glioblastoma tissues. We focused on the editing site within the miR-589-3p seed. MiR-589-3p is a unique miRNA almost fully edited (?100%) in normal brain and with a consistent editing decrease in glioblastoma. The edited version of miR-589-3p inhibits glioblastoma cell proliferation, migration and invasion, while the unedited version boosts cell proliferation and motility/invasion, thus being a potential cancer-promoting factor. We demonstrated that the editing of this miRNA is mediated by ADAR2, and retargets miR-589-3p from the tumor-suppressor PCDH9 to ADAM12, which codes for the metalloproteinase 12 promoting glioblastoma invasion. Overall, our study dissects the role of a unique brain-specific editing site within miR-589-3p, with important anticancer features, and highlights the importance of RNA editing as an essential player not only for diversifying the genomic message but also for correcting not-tolerable/critical genomic coding sites.

SUBMITTER: Cesarini V

PROVIDER: S-EPMC5829642 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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ADAR2/miR-589-3p axis controls glioblastoma cell migration/invasion.

Cesarini Valeriana V Silvestris Domenico A DA Tassinari Valentina V Tomaselli Sara S Alon Shahar S Eisenberg Eli E Locatelli Franco F Gallo Angela A

Nucleic acids research 20180201 4

Recent studies have reported the emerging role of microRNAs (miRNAs) in human cancers. We systematically characterized miRNA expression and editing in the human brain, which displays the highest number of A-to-I RNA editing sites among human tissues, and in de novo glioblastoma brain cancer. We identified 299 miRNAs altered in their expression and 24 miRNAs differently edited in human brain compared to glioblastoma tissues. We focused on the editing site within the miR-589-3p seed. MiR-589-3p is ...[more]

PMID: 29267965

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Project description:ObjectiveIn the present study, we tried to describe the role of miR-29c-3p in esophageal carcinoma (EC) and the relationship of miR-29c-3p with CCNA2 as well as cell cycle, accordingly revealing the potential molecular mechanism across cell proliferation, migration and invasion.MethodsExpression profiles of EC miRNAs and matched clinical data were accessed from TCGA database for differential and survival analyses. Bioinformatics databases were employed to predict the downstream targets of the potential miRNA, and enrichment analysis was performed on the miRNA and corresponding target gene using GSEA software. qRT-PCR was conducted to detect the expression levels of miR-29c-3p and CCNA2 mRNA in EC tissues and cells, and Western blot was performed for the examination of CCNA2, CDK1 and p53 protein levels. Subsequently, cells were harvested for MTT, Transwell as well as flow cytometry assays to examine cell viability, migration, invasion and cell cycle. Dual-luciferase reporter gene assay and RIP were carried out to further investigate and verify the targeted relationship between miR-29c-3p and CCNA2.ResultsMiR-29c-3p was shown to be significantly down-regulated in EC tissues and able to predict poor prognosis. CCNA2 was found to be a downstream target of miR-29c-3p and mainly enriched in cell cycle and p53 signaling pathway, whereas miR-29c-3p was remarkably activated in cell cycle. MiR-29c-3p overexpression inhibited cell proliferation, migration and invasion, as well as arrested cells in G0/G1 phase. As suggested by dual-luciferase reporter gene assay and RIP, CCNA2 was under the regulation of miR-29c-3p, and the negative correlation between the two genes was verified. Silencing CCNA2 could suppress cell proliferation, migration and invasion, as well as activate p53 pathway, even was seen to reverse the inhibitory effect of PFTβ on p53. Besides, in the presence of low miR-29c-3p, CCNA2 was up-regulated while p53 was simultaneously inhibited, resulting in the promotion of cell migration, invasion and cell cycle arrest.ConclusionMiR-29c-3p plays a regulatory role in EC tumorigenesis and development. MiR-29c-3p can target CCNA2 to mediate p53 signaling pathway, finally attributing to the inhibition of cell proliferation, migration and invasion, and making cells arrest in G0/G1 phase.

Dataset Information

ADAR2/miR-589-3p axis controls glioblastoma cell migration/invasion.

Publications

ADAR2/miR-589-3p axis controls glioblastoma cell migration/invasion.

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