Up-Regulation of Hsa-miR-11181 in Glioblastoma Multiforme as A Regulator of AKT and TGFBR1 Signalling

Document Type : Original Article

Authors

1 .Molecular Genetics Department, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

2 .Stem Cell and Regenerative Medicine Research Centre, Iran University of Medical Sciences (IUMS), Tehran, Iran

3 .Department of Neurosurgery, Shariati Hospital, Tehran University of Medical Science (TUMS), Tehran, Iran

Abstract

Objective
MicroRNAs (miRNAs) are short non-coding RNAs that play a role in post-transcriptional regulation of gene expression. Hsa-miR-11181 was originally introduced as a regulator of genes involved in some brain tumours. Due to the high expression of Hsa-miR-11181 in limited glioblastoma brain tumours, in this study we intend to assess the expressions of Hsa-miR-11181 and Has-miR11181-3p in brain tumour tissues and attribute new target genes to these miRNAs.
Materials and Methods
In this experimental study, total RNA from brain tissue samples was extracted for real-time quantitative polymerase chain reaction (RT-qPCR) analysis after cDNA synthesis. In order to confirm a direct interaction of Hsa-miR-11181 with two target genes, the 3ˊ UTR of AKT2 and transforming growth factor-beta receptor 1 (TGFBR1) were cloned separately for assessment by the dual luciferase assay.
Results
RT-qPCR analysis indicated that both Hsa-miR-11181-5p and Hsa-miR-11181-3p specifically up-regulated in higher grades of glioma tumours versus other brain tumour types. Consistently, lower expression levels of AKT2 and TGFBR1 were detected in higher grade gliomas compared to other types of brain tumours, which was inverse to the level of expression detected for the heparin-binding EGF-like growth factor (HBEGF) gene. The results of the dual luciferase assay supported a direct interaction of Hsa-miR-11181 with the 3ˊ UTR sequences of the AKT2 and TGFBR1 genes.
Conclusion
Overall, our data suggest that miR-1118 is a potential molecular biomarker for discrimination of glioma brain tumours from other brain tumour types.

Keywords