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Research Paper|Volume 9, Issue 3|pp 932—954

MiR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro and is directly targeting SMAD4, FRAT1 and BCL2

Tamara V. Werner1, Martin Hart1, Ruth Nickels2, Yoo-Jin Kim3, Michael D. Menger2, Rainer M. Bohle3, Andreas Keller4, Nicole Ludwig1, Eckart Meese1
  • 1Institute of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany
  • 2Institute for Clinical and Experimental Surgery, Medical School, Saarland University, 66421 Homburg/Saar, Germany
  • 3Institute of Pathology, Medical Center, Saarland University, 66421 Homburg/Saar, Germany
  • 4Clinical Bioinformatics, Saarland University, 66123 Saarbruecken, Germany
* These senior authors contributed equally to this paper
Received: February 28, 2017Accepted: March 3, 2017Published: March 23, 2017
https://doi.org/10.18632/aging.101201

Copyright: © 2017 Werner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Micro (mi)RNAs are short, noncoding RNAs and deregulation of miRNAs and their targets are implicated in tumor generation and progression in many cancers. Meningiomas are mostly benign, slow growing tumors of the central nervous system with a small percentage showing a malignant phenotype.

Following in silico prediction of potential targets of miR-34a-3p, SMAD4, FRAT1, and BCL2 have been confirmed as targets by dual luciferase assays with co-expression of miR-34a-3p and reporter gene constructs containing the respective 3’UTRs. Disruption of the miR-34a-3p binding sites in the 3’UTRs resulted in loss of responsiveness to miR-34a-3p overexpression. In meningioma cells, overexpression of miR-34a-3p resulted in decreased protein levels of SMAD4, FRAT1 and BCL2, while inhibition of miR-34a-3p led to increased levels of these proteins as confirmed by Western blotting. Furthermore, deregulation of miR-34a-3p altered cell proliferation and apoptosis of meningioma cells in vitro.

We show that SMAD4, FRAT1 and BCL2 are direct targets of miR-34a-3p and that deregulation of miR-34a-3p alters proliferation and apoptosis of meningioma cells in vitro. As part of their respective signaling pathways, which are known to play a role in meningioma genesis and progression, deregulation of SMAD4, FRAT1 and BCL2 might contribute to the aberrant activation of these signaling pathways leading to increased proliferation and inhibition of apoptosis in meningiomas.