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Published in: Cancer Cell International 1/2018

Open Access 01-12-2018 | Primary research

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

Authors: Eun Jung Sohn, Kyoung-mi Bak, Yun-kyeong Nam, Hwan Tae Park

Published in: Cancer Cell International | Issue 1/2018

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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.
Literature
1.
go back to reference Fuller GN. The WHO classification of tumours of the central nervous system, 4th edition. Arch Pathol Lab Med. 2008;132:906.PubMed Fuller GN. The WHO classification of tumours of the central nervous system, 4th edition. Arch Pathol Lab Med. 2008;132:906.PubMed
2.
go back to reference Celis-Aguilar E, Lassaletta L, Torres-Martin M, et al. The molecular biology of vestibular schwannomas and its association with hearing loss: a review. Genet Res Int. 2012;2012:856157.PubMedPubMedCentral Celis-Aguilar E, Lassaletta L, Torres-Martin M, et al. The molecular biology of vestibular schwannomas and its association with hearing loss: a review. Genet Res Int. 2012;2012:856157.PubMedPubMedCentral
3.
go back to reference Sade R, Calikoglu C, Cakir M, et al. Very rare reason of neurologic deficit: thoracic cystic schwannoma. Spine J. 2015;15:1897–8.CrossRefPubMed Sade R, Calikoglu C, Cakir M, et al. Very rare reason of neurologic deficit: thoracic cystic schwannoma. Spine J. 2015;15:1897–8.CrossRefPubMed
4.
go back to reference Hung CH, Tsai TH, Lieu AS, et al. Giant invasive schwannoma of cauda equina with minimal neurologic deficit: a case report and literature review. Kaohsiung J Med Sci. 2008;24:212–7.CrossRefPubMed Hung CH, Tsai TH, Lieu AS, et al. Giant invasive schwannoma of cauda equina with minimal neurologic deficit: a case report and literature review. Kaohsiung J Med Sci. 2008;24:212–7.CrossRefPubMed
5.
go back to reference Petrilli AM, Fernandez-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2016;35:537–48.CrossRefPubMed Petrilli AM, Fernandez-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2016;35:537–48.CrossRefPubMed
7.
go back to reference Srimal RC, Dhawan BN. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol. 1973;25:447–52.CrossRefPubMed Srimal RC, Dhawan BN. Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent. J Pharm Pharmacol. 1973;25:447–52.CrossRefPubMed
8.
go back to reference Yun DG, Lee DG. Antibacterial activity of curcumin via apoptosis-like response in Escherichia coli. Appl Microbiol Biotechnol. 2016;100:5505–14.CrossRefPubMed Yun DG, Lee DG. Antibacterial activity of curcumin via apoptosis-like response in Escherichia coli. Appl Microbiol Biotechnol. 2016;100:5505–14.CrossRefPubMed
9.
go back to reference Seehofer D, Schirmeier A, Bengmark S, et al. Curcumin attenuates oxidative stress and inflammatory response in the early phase after partial hepatectomy with simultaneous intraabdominal infection in rats. J Surg Res. 2010;159:497–502.CrossRefPubMed Seehofer D, Schirmeier A, Bengmark S, et al. Curcumin attenuates oxidative stress and inflammatory response in the early phase after partial hepatectomy with simultaneous intraabdominal infection in rats. J Surg Res. 2010;159:497–502.CrossRefPubMed
10.
go back to reference Sandhir R, Yadav A, Mehrotra A, et al. Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington’s disease. Neuromol Med. 2014;16:106–18.CrossRef Sandhir R, Yadav A, Mehrotra A, et al. Curcumin nanoparticles attenuate neurochemical and neurobehavioral deficits in experimental model of Huntington’s disease. Neuromol Med. 2014;16:106–18.CrossRef
13.
go back to reference He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.CrossRefPubMed He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31.CrossRefPubMed
14.
go back to reference Sharma P, Sharma R. miRNA-mRNA crosstalk in esophageal cancer: from diagnosis to therapy. Crit Rev Oncol Hematol. 2015;96:449–62.CrossRefPubMed Sharma P, Sharma R. miRNA-mRNA crosstalk in esophageal cancer: from diagnosis to therapy. Crit Rev Oncol Hematol. 2015;96:449–62.CrossRefPubMed
15.
go back to reference Orellana EA, Kasinski AL. MicroRNAs in cancer: a historical perspective on the path from discovery to therapy. Cancers (Basel). 2015;7:1388–405.CrossRef Orellana EA, Kasinski AL. MicroRNAs in cancer: a historical perspective on the path from discovery to therapy. Cancers (Basel). 2015;7:1388–405.CrossRef
16.
go back to reference Muhammad N, Bhattacharya S, Steele R, et al. Anti-miR-203 suppresses ER-positive breast cancer growth and stemness by targeting SOCS3. Oncotarget. 2016;7:58595–605.CrossRefPubMedPubMedCentral Muhammad N, Bhattacharya S, Steele R, et al. Anti-miR-203 suppresses ER-positive breast cancer growth and stemness by targeting SOCS3. Oncotarget. 2016;7:58595–605.CrossRefPubMedPubMedCentral
18.
go back to reference Xie M, Dart DA, Guo T, et al. MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer. Gastric Cancer. 2018;21:41–54.CrossRefPubMed Xie M, Dart DA, Guo T, et al. MicroRNA-1 acts as a tumor suppressor microRNA by inhibiting angiogenesis-related growth factors in human gastric cancer. Gastric Cancer. 2018;21:41–54.CrossRefPubMed
19.
20.
go back to reference Liu K, Sun X, Zhang Y, et al. MiR-598: a tumor suppressor with biomarker significance in osteosarcoma. Life Sci. 2017;188:141–8.CrossRefPubMed Liu K, Sun X, Zhang Y, et al. MiR-598: a tumor suppressor with biomarker significance in osteosarcoma. Life Sci. 2017;188:141–8.CrossRefPubMed
21.
go back to reference Sohn EJ, Won G, Lee J, et al. Upregulation of miRNA3195 and miRNA374b mediates the anti-angiogenic properties of melatonin in hypoxic PC-3 prostate cancer cells. J Cancer. 2015;6:19–28.CrossRefPubMedPubMedCentral Sohn EJ, Won G, Lee J, et al. Upregulation of miRNA3195 and miRNA374b mediates the anti-angiogenic properties of melatonin in hypoxic PC-3 prostate cancer cells. J Cancer. 2015;6:19–28.CrossRefPubMedPubMedCentral
22.
go back to reference Momtazi AA, Shahabipour F, Khatibi S, et al. Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol. 2016;171:1–38.CrossRefPubMed Momtazi AA, Shahabipour F, Khatibi S, et al. Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol. 2016;171:1–38.CrossRefPubMed
23.
go back to reference Czabotar PE, Lessene G, Strasser A, et al. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15:49–63.CrossRefPubMed Czabotar PE, Lessene G, Strasser A, et al. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15:49–63.CrossRefPubMed
24.
go back to reference Lopez-Lazaro M. Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol Nutr Food Res. 2008;52(Suppl 1):S103–27.PubMed Lopez-Lazaro M. Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent. Mol Nutr Food Res. 2008;52(Suppl 1):S103–27.PubMed
25.
go back to reference Angelo LS, Wu JY, Meng F, et al. Combining curcumin (diferuloylmethane) and heat shock protein inhibition for neurofibromatosis 2 treatment: analysis of response and resistance pathways. Mol Cancer Ther. 2011;10:2094–103.CrossRefPubMed Angelo LS, Wu JY, Meng F, et al. Combining curcumin (diferuloylmethane) and heat shock protein inhibition for neurofibromatosis 2 treatment: analysis of response and resistance pathways. Mol Cancer Ther. 2011;10:2094–103.CrossRefPubMed
26.
go back to reference Angelo LS, Maxwell DS, Wu JY, et al. Binding partners for curcumin in human schwannoma cells: biologic implications. Bioorg Med Chem. 2013;21:932–9.CrossRefPubMed Angelo LS, Maxwell DS, Wu JY, et al. Binding partners for curcumin in human schwannoma cells: biologic implications. Bioorg Med Chem. 2013;21:932–9.CrossRefPubMed
27.
go back to reference Zhou X, Chen J, Xiao Q, et al. MicroRNA-638 inhibits cell growth and tubule formation by suppressing VEGFA expression in human Ewing sarcoma cells. Biosci Rep. 2018;38:1017. Zhou X, Chen J, Xiao Q, et al. MicroRNA-638 inhibits cell growth and tubule formation by suppressing VEGFA expression in human Ewing sarcoma cells. Biosci Rep. 2018;38:1017.
28.
go back to reference Tahiri A, Aure MR, Kristensen VN. MicroRNA networks in breast cancer cells. Methods Mol Biol. 2018;1711:55–81.CrossRefPubMed Tahiri A, Aure MR, Kristensen VN. MicroRNA networks in breast cancer cells. Methods Mol Biol. 2018;1711:55–81.CrossRefPubMed
29.
go back to reference Wang G, Fang X, Han M, et al. MicroRNA-493-5p promotes apoptosis and suppresses proliferation and invasion in liver cancer cells by targeting VAMP2. Int J Mol Med. 2018;41:1740–8.PubMed Wang G, Fang X, Han M, et al. MicroRNA-493-5p promotes apoptosis and suppresses proliferation and invasion in liver cancer cells by targeting VAMP2. Int J Mol Med. 2018;41:1740–8.PubMed
30.
go back to reference Torres-Martin M, Lassaletta L, de Campos JM, et al. Global profiling in vestibular schwannomas shows critical deregulation of microRNAs and upregulation in those included in chromosomal region 14q32. PLoS ONE. 2013;8:e65868.CrossRefPubMedPubMedCentral Torres-Martin M, Lassaletta L, de Campos JM, et al. Global profiling in vestibular schwannomas shows critical deregulation of microRNAs and upregulation in those included in chromosomal region 14q32. PLoS ONE. 2013;8:e65868.CrossRefPubMedPubMedCentral
31.
go back to reference Saydam O, Senol O, Wurdinger T, et al. miRNA-7 attenuation in Schwannoma tumors stimulates growth by upregulating three oncogenic signaling pathways. Cancer Res. 2011;71:852–61.CrossRefPubMed Saydam O, Senol O, Wurdinger T, et al. miRNA-7 attenuation in Schwannoma tumors stimulates growth by upregulating three oncogenic signaling pathways. Cancer Res. 2011;71:852–61.CrossRefPubMed
32.
go back to reference Ma J, Li T, Yuan H, et al. MicroRNA-29a inhibits proliferation and motility of schwannoma cells by targeting CDK6. J Cell Biochem. 2018;119:2617–26.CrossRefPubMed Ma J, Li T, Yuan H, et al. MicroRNA-29a inhibits proliferation and motility of schwannoma cells by targeting CDK6. J Cell Biochem. 2018;119:2617–26.CrossRefPubMed
33.
go back to reference Cioffi JA, Yue WY, Mendolia-Loffredo S, et al. MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival. Otol Neurotol. 2010;31:1455–62.PubMedPubMedCentral Cioffi JA, Yue WY, Mendolia-Loffredo S, et al. MicroRNA-21 overexpression contributes to vestibular schwannoma cell proliferation and survival. Otol Neurotol. 2010;31:1455–62.PubMedPubMedCentral
34.
go back to reference Norouzi S, Majeed M, Pirro M, et al. Curcumin as an adjunct therapy and microRNA modulator in breast cancer. Curr Pharm Des. 2017;24:171–7.CrossRef Norouzi S, Majeed M, Pirro M, et al. Curcumin as an adjunct therapy and microRNA modulator in breast cancer. Curr Pharm Des. 2017;24:171–7.CrossRef
35.
go back to reference Mirzaei H, Masoudifar A, Sahebkar A, et al. MicroRNA: a novel target of curcumin in cancer therapy. J Cell Physiol. 2018;233:3004–15.CrossRefPubMed Mirzaei H, Masoudifar A, Sahebkar A, et al. MicroRNA: a novel target of curcumin in cancer therapy. J Cell Physiol. 2018;233:3004–15.CrossRefPubMed
36.
go back to reference Ma J, Fang B, Zeng F, et al. Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells. Toxicol Lett. 2014;231:82–91.CrossRefPubMed Ma J, Fang B, Zeng F, et al. Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells. Toxicol Lett. 2014;231:82–91.CrossRefPubMed
37.
go back to reference Li W, Yang W, Liu Y, et al. MicroRNA-378 enhances inhibitory effect of curcumin on glioblastoma. Oncotarget. 2017;8:73938–46.PubMedPubMedCentral Li W, Yang W, Liu Y, et al. MicroRNA-378 enhances inhibitory effect of curcumin on glioblastoma. Oncotarget. 2017;8:73938–46.PubMedPubMedCentral
38.
go back to reference Yang J, Cao Y, Sun J, et al. Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells. Med Oncol. 2010;27:1114–8.CrossRefPubMed Yang J, Cao Y, Sun J, et al. Curcumin reduces the expression of Bcl-2 by upregulating miR-15a and miR-16 in MCF-7 cells. Med Oncol. 2010;27:1114–8.CrossRefPubMed
39.
go back to reference Jin H, Qiao F, Wang Y, et al. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep. 2015;34:2782–9.CrossRefPubMed Jin H, Qiao F, Wang Y, et al. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep. 2015;34:2782–9.CrossRefPubMed
Metadata
Title
Upregulation of microRNA 344a-3p is involved in curcumin induced apoptosis in RT4 schwannoma cells
Authors
Eun Jung Sohn
Kyoung-mi Bak
Yun-kyeong Nam
Hwan Tae Park
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2018
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-018-0693-x

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