MiR-34a-3p alters proliferation and apoptosis of meningioma cellsin vitroand is directly targeting SMAD4, FRAT1 and BCL2.
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.Followingin silicoprediction of potential targets of miR-34a-3p,SMAD4,FRAT1, andBCL2have 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 cellsin vitro.We show thatSMAD4,FRAT1andBCL2are direct targets of miR-34a-3p and that deregulation of miR-34a-3p alters proliferation and apoptosis of meningioma cellsin vitro. As part of their respective signaling pathways, which are known to play a role in meningioma genesis and progression, deregulation ofSMAD4,FRAT1andBCL2might contribute to the aberrant activation of these signaling pathways leading to increased proliferation and inhibition of apoptosis in meningiomas.
Institute of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
Tamara V
TV
Werner
Institute of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
Martin
M
Hart
Institute for Clinical and Experimental Surgery, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
Ruth
R
Nickels
Institute of Pathology, Medical Center, Saarland University, 66421 Homburg/Saar, Germany.
Yoo-Jin
YJ
Kim
Institute for Clinical and Experimental Surgery, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
Michael D
MD
Menger
Institute of Pathology, Medical Center, Saarland University, 66421 Homburg/Saar, Germany.
Rainer M
RM
Bohle
Clinical Bioinformatics, Saarland University, 66123 Saarbruecken, Germany.
Andreas
A
Keller
Institute of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
Nicole
N
Ludwig
Institute of Human Genetics, Medical School, Saarland University, 66421 Homburg/Saar, Germany.
Eckart
E
Meese
D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D003198:Computer Simulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; C000595707:BCL2 protein, human; C491819:FRAT1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051901:Smad4 Protein
BCL2; FRAT1; SMAD4; meningioma; miR-34a-3p