Novel internal regulators and candidate miRNAs within miR-379/miR-656 miRNA cluster can alter cellular phenotype of human glioblastoma

Nayak, S, Aich, M, Kumar, A, Sengupta, S, Bajad, P, Dhapola, P, Paul, D, Narta, K, Purkrait, S, Mehani, B, Suri, A, Chakraborty, D, Mukhopadhyay, A ORCID: 0000-0002-1089-7179 and Sarkar, C 2018, 'Novel internal regulators and candidate miRNAs within miR-379/miR-656 miRNA cluster can alter cellular phenotype of human glioblastoma' , Scientific Reports, 8 (2018) , #7673.

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Abstract

Clustered miRNAs can affect functioning of downstream pathways due to possible coordinated function. We observed 78-88% of the miR-379/miR-656 cluster (C14MC) miRNAs were downregulated in three sub-types of diffuse gliomas, which was also corroborated with analysis from The Cancer Genome Atlas (TCGA) datasets. The miRNA expression levels decreased with increasing tumor grade, indicating this downregulation as an early event in gliomagenesis. Higher expression of the C14MC miRNAs significantly improved glioblastioma prognosis (Pearson’s r=0.62; p<3.08e-22). ENCODE meta-data analysis, followed by reporter assays validated existence of two novel internal regulators within C14MC. CRISPR activation of the most efficient internal regulator specifically induced members of the downstream miRNA sub-cluster and apoptosis in glioblastoma cells. Luciferase assays validated novel targets for miR-134 and miR-485-5p, two miRNAs from C14MC with the most number of target genes relevant for glioma. Overexpression of miR-134 and miR-485-5p in human glioblastoma cells suppressed invasion and proliferation, respectively. Furthermore, apoptosis was induced by both miRs, individually and in combination. The results emphasize the tumor suppressive role of C14MC in diffuse gliomas, and identifies two specific miRNAs with potential therapeutic value and towards better disease management and therapy.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Scientific Reports
Publisher: Nature Publishing Group
ISSN: 2045-2322
Related URLs:
Funders: Department of Biotechnology (DBT), Government of India, Council of Scientific and Industrial Research (CSIR), Government of India, Cardio-Neurosciences Centre (AIIMS, New Delhi)
Depositing User: USIR Admin
Date Deposited: 24 Apr 2018 07:39
Last Modified: 18 Aug 2018 19:32
URI: http://usir.salford.ac.uk/id/eprint/46825

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