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

Scientific Reports
Subhashree NayakChitra Sarkar

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...Continue Reading

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Citations

Aug 23, 2019·Wiley Interdisciplinary Reviews. RNA·Shama Prasada KabekkoduKapaettu Satyamoorthy
Dec 10, 2019·Clinical & Experimental Metastasis·Padacherri Vethil JishnuShama Prasada Kabekkodu
Mar 17, 2021·Experimental Cell Research·Lei ChengYiwei Liao
Mar 25, 2021·Computational Biology and Chemistry·Yazdan RahmatiHasan Mollanoori
Apr 13, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Soudeh Ghafouri-FardSeyed Ali Mousavinejad
Oct 31, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuelong ZhangQi Zhang

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Methods Mentioned

BETA
Low
RNA-Seq
transfection
PCR
RNA Seq
Assay

Software Mentioned

package
Python
Scipy
Lifelines
R package
CRISPRSCAN
UCSC Genome Browser
custom Python scripts
Scipy package

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