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MicroRNA-10b is overexpressed and critical for cell survival and proliferation in medulloblastoma

Pal, R and Greene, S (2015) MicroRNA-10b is overexpressed and critical for cell survival and proliferation in medulloblastoma. PLoS ONE, 10 (9).

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Abstract

This study demonstrates the effects of miRNA-10b on medulloblastoma proliferation through transcriptional induction of the anti-apoptotic protein BCL2. Using a cancer specific miRNAarray, high expression of miRNA-10b inmedulloblastoma cell lines compared to a normal cerebellar control was shown, and this was confirmed with real time PCR (RT-PCR). Two medulloblastoma cell lines (DAOY and UW228) were transiently transfected with control miRNA, miRNA-10b inhibitor or miRNA-10bmimic and subjected to RT-PCR, MTT, apoptosis, clonogenic assay and western blot analysis. Transfection ofmiRNA-10b inhibitor induced a significant down-regulation of miRNA-10b expression, inhibited proliferation, and induced apoptosis, while miRNA-10b mimic exerted an opposite effect. Inhibition of miRNA-10b abrogated the colony-forming capability of medulloblastoma cells, andmarkedly down-regulated the expression of BCL2. Down-regulation of BCL2 by antisense oligonucleotides or siRNA also significantly down-regulated miRNA-10b, suggesting that BCL2 is a major mediator of the effects of miRNA-10b. ABT-737 and ABT-199, potent inhibitors of BCL2, downregulated the expression of miRNA-10b and increased apoptosis. Analysis ofmiRNA-10b levels in 13 primary medulloblastoma samples revealed that the 2 patients with the highest levels of miRNA-10b had multiple recurrences (4.5) and died within 8 years of diagnosis, compared with the 11 patients with low levels of miRNA-10b who had a mean of 1.2 recurrences and nearly 40% long-term survival. The data presented here indicate that miRNA-10b may act as an oncomir in medulloblastoma tumorigenesis, and reveal a previously unreported mechanismwith Bcl-2 as a mediator of the effects of miRNA-10b upon medulloblastoma cell survival.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Pal, R
Greene, S
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorRoemer, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 22 September 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 10
Number: 9
DOI or Unique Handle: 10.1371/journal.pone.0137845
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Neurological Surgery
Refereed: Yes
Date Deposited: 23 Aug 2016 14:38
Last Modified: 03 Apr 2021 19:55
URI: http://d-scholarship.pitt.edu/id/eprint/28383

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