Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells

Abstract Background Schwannoma arising from peripheral nervous sheaths is a benign tumor. Methods To evaluate cell cytotoxicity, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction and terminal deoxynucleotidyltransferase UTP nick-end labeling (TUNEL) assays were use...

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Main Authors: Eun Jung Sohn, Kyoung-mi Bak, Yun-kyeong Nam, Hwan Tae Park
Format: Article
Language:English
Published: BMC 2018-12-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-018-0693-x
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author Eun Jung Sohn
Kyoung-mi Bak
Yun-kyeong Nam
Hwan Tae Park
author_facet Eun Jung Sohn
Kyoung-mi Bak
Yun-kyeong Nam
Hwan Tae Park
author_sort Eun Jung Sohn
collection DOAJ
description Abstract Background Schwannoma arising from peripheral nervous sheaths is a benign tumor. Methods To evaluate cell cytotoxicity, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction and terminal deoxynucleotidyltransferase UTP nick-end labeling (TUNEL) assays were used. A microRNA (miRNA) array was used to identify the miRNAs involved in curcumin-induced apoptosis. To examine miRNA expression, quantitative RT-PCR was used. Results In this study, curcumin exerted cellular cytotoxicity against RT4 schwannoma cells, with an increase in TUNEL-positive cells. Curcumin also activated the expression of apoptotic proteins, such as polyADP ribose polymerase, caspase-3, and caspase-9. The miRNA array revealed that seven miRNAs (miRNA 350, miRNA 17-2-3p, let 7e-3p, miRNA1224, miRNA 466b-1-3p, miRNA 18a-5p, and miRNA 322-5p) were downregulated following treatment with both 10 and 20 μM curcumin in RT4 cells, while four miRNAs (miRNA122-5p, miRNA 3473, miRNA182, and miRNA344a-3p) were upregulated. Interestingly, transfection with a miRNA 344a-3p mimic downregulated the mRNA expression of Bcl2 and upregulated that of Bax, Curcumin treatment in RT 4 cells also reduced the mRNA expression of Bcl2 and enhanced expression of Bax, Overexpression of miRNA344a-3p mimic combined with curcumin treatment activated the expression of apoptotic proteins, including procaspase-9 and cleaved caspase-3 while inhibition of miRNA 344a-3p using miR344a-3p inhibitor repressed cleaved caspase-3 and -9 in curcumin treated RT-4 cells compared to control. Conclusions Our findings demonstrate that curcumin induces apoptosis in schwannoma cells via miRNA 344a-3p. Thus, curcumin may serve as a potent therapeutic agent for the treatment of schwannoma.
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spelling doaj.art-190574cbda4f4a1a80a6ea5771e3bba22022-12-22T01:25:52ZengBMCCancer Cell International1475-28672018-12-0118111010.1186/s12935-018-0693-xUpregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cellsEun Jung Sohn0Kyoung-mi Bak1Yun-kyeong Nam2Hwan Tae Park3Peripheral Neuropathy Research Center, Department of Molecular Neuroscience, College of Medicine, Dong-A UniversityPeripheral Neuropathy Research Center, Department of Molecular Neuroscience, College of Medicine, Dong-A UniversityPeripheral Neuropathy Research Center, Department of Molecular Neuroscience, College of Medicine, Dong-A UniversityPeripheral Neuropathy Research Center, Department of Molecular Neuroscience, College of Medicine, Dong-A UniversityAbstract Background Schwannoma arising from peripheral nervous sheaths is a benign tumor. Methods To evaluate cell cytotoxicity, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction and terminal deoxynucleotidyltransferase UTP nick-end labeling (TUNEL) assays were used. A microRNA (miRNA) array was used to identify the miRNAs involved in curcumin-induced apoptosis. To examine miRNA expression, quantitative RT-PCR was used. Results In this study, curcumin exerted cellular cytotoxicity against RT4 schwannoma cells, with an increase in TUNEL-positive cells. Curcumin also activated the expression of apoptotic proteins, such as polyADP ribose polymerase, caspase-3, and caspase-9. The miRNA array revealed that seven miRNAs (miRNA 350, miRNA 17-2-3p, let 7e-3p, miRNA1224, miRNA 466b-1-3p, miRNA 18a-5p, and miRNA 322-5p) were downregulated following treatment with both 10 and 20 μM curcumin in RT4 cells, while four miRNAs (miRNA122-5p, miRNA 3473, miRNA182, and miRNA344a-3p) were upregulated. Interestingly, transfection with a miRNA 344a-3p mimic downregulated the mRNA expression of Bcl2 and upregulated that of Bax, Curcumin treatment in RT 4 cells also reduced the mRNA expression of Bcl2 and enhanced expression of Bax, Overexpression of miRNA344a-3p mimic combined with curcumin treatment activated the expression of apoptotic proteins, including procaspase-9 and cleaved caspase-3 while inhibition of miRNA 344a-3p using miR344a-3p inhibitor repressed cleaved caspase-3 and -9 in curcumin treated RT-4 cells compared to control. Conclusions Our findings demonstrate that curcumin induces apoptosis in schwannoma cells via miRNA 344a-3p. Thus, curcumin may serve as a potent therapeutic agent for the treatment of schwannoma.http://link.springer.com/article/10.1186/s12935-018-0693-xCurcuminMicroRNASchwannomaRT4
spellingShingle Eun Jung Sohn
Kyoung-mi Bak
Yun-kyeong Nam
Hwan Tae Park
Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells
Cancer Cell International
Curcumin
MicroRNA
Schwannoma
RT4
title Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells
title_full Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells
title_fullStr Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells
title_full_unstemmed Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells
title_short Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells
title_sort upregulation of microrna 344a 3p is involved in curcumin induced apoptosis in rt4 schwannoma cells
topic Curcumin
MicroRNA
Schwannoma
RT4
url http://link.springer.com/article/10.1186/s12935-018-0693-x
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