Curcumin enhances the radiosensitivity in nasopharyngeal carcinoma cells involving the reversal of differentially expressed long non-coding RNAs

Wang,Qirui; Fan,Haoning; Liu,Ying; Yin,Zhixin; Cai,Hongbing; Liu,Jie; Wang,Zhiyuan; Shao,Meng; Sun,Xuegang; Diao,Jianxin; Liu,Yuanliang; Tong,Li; Fan,Qin

doi:10.3892/ijo.2013.2237

Curcumin enhances the radiosensitivity in nasopharyngeal carcinoma cells involving the reversal of differentially expressed long non-coding RNAs

Authors:
- Qirui Wang
- Haoning Fan
- Ying Liu
- Zhixin Yin
- Hongbing Cai
- Jie Liu
- Zhiyuan Wang
- Meng Shao
- Xuegang Sun
- Jianxin Diao
- Yuanliang Liu
- Li Tong
- Qin Fan
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Affiliations: College of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, P.R. China, Department of Radiotherapy, NanFang Hospital, Southern Medical University, Guangzhou 510515, P.R. China, Institute of Genetic Engineering, Southern Medical University, Guangzhou 510515, P.R. China
Published online on: December 30, 2013 https://doi.org/10.3892/ijo.2013.2237
Pages: 858-864

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Abstract

Long non-coding RNAs (lncRNAs) are aberrantly expressed and have important functions in pathological processes. The present study investigated the lncRNA profiles and the effects of curcumin (Cur) on the radiosensitivity of nasopharyngeal carcinoma (NPC) cells. The lncRNA and mRNA profiles of each cell group were described by microarray analysis. Numerous differentially expressed genes were observed by microarrays in three cell groups. Cur significantly reversed the IR-induced lncRNA and mRNA expression signatures, shown by clustering analysis. Moreover, 116 of these IR-induced and Cur-reversed differentially expressed lncRNAs were obtained. Six lncRNAs (AF086415, AK095147, RP1-179N16.3, MUDENG, AK056098 and AK294004) were confirmed by qPCR. Furthermore, functional studies showed that lncRNA AK294004 exhibited a negative effect on cyclin D1 (CCND1), indicating that CCND1 might be a direct target of AK294004. IR-induced differentially expressed lncRNAs were reversed during Cur-enhanced radiosensitization in NPC cells, suggesting that lncRNAs have important functions in IR-induced radioresistance. Thus, Cur could serve as a good radiosensitizer.

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1.	Ou J, Pan F, Geng P, et al: Silencing fibronectin extra domain A enhances radiosensitivity in nasopharyngeal carcinomas involving an FAK/Akt/JNK pathway. Int J Radiat Oncol Biol Phys. 82:e685–e691. 2012. View Article : Google Scholar : PubMed/NCBI
2.	Lu ZX, Ma XQ, Yang LF, et al: DNAzymes targeted to EBV-encoded latent membrane protein-1 induce apoptosis and enhance radiosensitivity in nasopharyngeal carcinoma. Cancer Lett. 265:226–238. 2008. View Article : Google Scholar : PubMed/NCBI
3.	Ou J, Luan W, Deng J, Sa R and Liang H: αv integrin induces multicellular radioresistance in human nasopharyngeal carcinoma via activating SAPK/JNK pathway. PLoS One. 7:e387372012.
4.	Bernier J: A multidisciplinary approach to squamous cell carcinomas of the head and neck: an update. Curr Opin Oncol. 20:249–255. 2008. View Article : Google Scholar : PubMed/NCBI
5.	Feng XP, Yi H, Li MY, et al: Identification of biomarkers for predicting nasopharyngeal carcinoma response to radiotherapy by proteomics. Cancer Res. 70:3450–3462. 2010. View Article : Google Scholar : PubMed/NCBI
6.	Sandur SK, Deorukhkar A, Pandey MK, et al: Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kappaB activity. Int J Radiat Oncol Biol Phys. 75:534–542. 2009. View Article : Google Scholar : PubMed/NCBI
7.	Shishodia S, Amin HM, Lai R and Aggarwal BB: Curcumin (diferuloylmethane) inhibits constitutive NF-kappaB activation, induces G1/S arrest, suppresses proliferation, and induces apoptosis in mantle cell lymphoma. Biochem Pharmacol. 70:700–713. 2005. View Article : Google Scholar
8.	Li L, Aggarwal BB, Shishodia S, Abbruzzese J and Kurzrock R: Nuclear factor-kappaB and IkappaB kinase are constitutively active in human pancreatic cells, and their down-regulation by curcumin (diferuloylmethane) is associated with the suppression of proliferation and the induction of apoptosis. Cancer. 101:2351–2362. 2004. View Article : Google Scholar
9.	Bharti AC, Shishodia S, Reuben JM, et al: Nuclear factor-kappaB and STAT3 are constitutively active in CD138⁺ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood. 103:3175–3184. 2004.PubMed/NCBI
10.	Wang X, Xia X, Xu C, et al: Ultrasound-induced cell death of nasopharyngeal carcinoma cells in the presence of curcumin. Integr Cancer Ther. 10:70–76. 2011. View Article : Google Scholar : PubMed/NCBI
11.	Wong TS, Chan WS, Li CH, et al: Curcumin alters the migratory phenotype of nasopharyngeal carcinoma cells through up-regulation of E-cadherin. Anticancer Res. 30:2851–2856. 2010.PubMed/NCBI
12.	Zhang X, Sun S, Pu JK, et al: Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis. 48:1–8. 2012. View Article : Google Scholar : PubMed/NCBI
13.	Kaikkonen MU, Lam MT and Glass CK: Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res. 90:430–440. 2011. View Article : Google Scholar : PubMed/NCBI
14.	Mercer TR, Dinger ME and Mattick JS: Long non-coding RNAs: insights into functions. Nat Rev Genet. 10:155–159. 2009. View Article : Google Scholar : PubMed/NCBI
15.	Wang KC and Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell. 43:904–914. 2011. View Article : Google Scholar
16.	Nagano T and Fraser P: No-nonsense functions for long noncoding RNAs. Cell. 145:178–181. 2011. View Article : Google Scholar : PubMed/NCBI
17.	Ozgur E, Mert U, Isin M, Okutan M, Dalay N and Gezer U: Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells. Clin Exp Med. 13:119–126. 2013. View Article : Google Scholar : PubMed/NCBI
18.	Barsyte-Lovejoy D, Lau SK, Boutros PC, et al: The c-Myc oncogene directly induces the H19 noncoding RNA by allele-specific binding to potentiate tumorigenesis. Cancer Res. 66:5330–5337. 2006. View Article : Google Scholar : PubMed/NCBI
19.	Zhou Y, Zhong Y, Wang Y, et al: Activation of p53 by MEG3 non-coding RNA. J Biol Chem. 282:24731–24742. 2007. View Article : Google Scholar : PubMed/NCBI
20.	Mariner PD, Walters RD, Espinoza CA, et al: Human Alu RNA is a modular transacting repressor of mRNA transcription during heat shock. Mol Cell. 29:499–509. 2008. View Article : Google Scholar : PubMed/NCBI
21.	Beltran M, Puig I, Pena C, et al: A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1-induced epithelial-mesenchymal transition. Genes Dev. 22:756–769. 2008. View Article : Google Scholar : PubMed/NCBI
22.	Gupta RA, Shah N, Wang KC, et al: Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature. 464:1071–1076. 2010. View Article : Google Scholar : PubMed/NCBI
23.	Huarte M and Rinn JL: Large non-coding RNAs: missing links in cancer? Hum Mol Genet. 19:R152–R161. 2010. View Article : Google Scholar : PubMed/NCBI
24.	Wang J, Guo LP, Chen LZ, Zeng YX and Lu SH: Identification of cancer stem cell-like side population cells in human nasopharyngeal carcinoma cell line. Cancer Res. 67:3716–3724. 2007. View Article : Google Scholar : PubMed/NCBI
25.	Huang da W, Sherman BT and Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 37:1–13. 2009.PubMed/NCBI
26.	Fan Q, He M, Deng X, et al: Derepression of c-Fos caused by MicroRNA-139 down-regulation contributes to the metastasis of human hepatocellular carcinoma. Cell Biochem Funct. 31:319–324. 2013. View Article : Google Scholar : PubMed/NCBI
27.	Liu Y, Cai H, Liu J, et al: A miR-151 binding site polymorphism in the 3′-untranslated region of the cyclin E1 gene associated with nasopharyngeal carcinoma. Biochem Biophys Res Commun. 432:660–665. 2013.PubMed/NCBI
28.	Pearce AG, Segura TM, Rintala AC, Rintala-Maki ND and Lee H: The generation and characterization of a radiation-resistant model system to study radioresistance in human breast cancer cells. Radiat Res. 156:739–750. 2001. View Article : Google Scholar : PubMed/NCBI
29.	Baldwin AS: Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J Clin Invest. 107:241–246. 2001. View Article : Google Scholar : PubMed/NCBI
30.	Singh S and Aggarwal BB: Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane) [corrected]. J Biol Chem. 270:24995–25000. 1995.
31.	Li JY, Li YY, Jin W, Yang Q, Shao ZM and Tian XS: ABT-737 reverses the acquired radioresistance of breast cancer cells by targeting Bcl-2 and Bcl-xL. J Exp Clin Cancer Res. 31:1022012. View Article : Google Scholar : PubMed/NCBI
32.	Kunnumakkara AB, Diagaradjane P, Guha S, et al: Curcumin sensitizes human colorectal cancer xenografts in nude mice to gamma-radiation by targeting nuclear factor-kappaB-regulated gene products. Clin Cancer Res. 14:2128–2136. 2008. View Article : Google Scholar
33.	Javvadi P, Segan AT, Tuttle SW and Koumenis C: The chemo-preventive agent curcumin is a potent radiosensitizer of human cervical tumor cells via increased reactive oxygen species production and overactivation of the mitogen-activated protein kinase pathway. Mol Pharmacol. 73:1491–1501. 2008. View Article : Google Scholar
34.	Narang H and Krishna M: Inhibition of radiation induced nitration by curcumin and nicotinamide in mouse macrophages. Mol Cell Biochem. 276:7–13. 2005. View Article : Google Scholar : PubMed/NCBI
35.	Hannoun-Levi JM, Chand-Fouche ME, Dejean C and Courdi A: Dose gradient impact on equivalent dose at 2 Gy for high dose rate interstitial brachytherapy. J Contemp Brachytherapy. 4:14–20. 2012. View Article : Google Scholar : PubMed/NCBI
36.	Khalil AM, Guttman M, Huarte M, et al: Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci USA. 106:11667–11672. 2009. View Article : Google Scholar
37.	Guttman M, Amit I, Garber M, et al: Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature. 458:223–227. 2009. View Article : Google Scholar : PubMed/NCBI
38.	Wang X, Arai S, Song X, et al: Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. 454:126–130. 2008. View Article : Google Scholar : PubMed/NCBI
39.	Aravindan N, Veeraraghavan J, Madhusoodhanan R, Herman TS and Natarajan M: Curcumin regulates low-linear energy transfer gamma-radiation-induced NFkappaB-dependent telomerase activity in human neuroblastoma cells. Int J Radiat Oncol Biol Phys. 79:1206–1215. 2011. View Article : Google Scholar
40.	Forrester HB, Li J, Hovan D, Ivashkevich AN and Sprung CN: DNA repair genes: alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation. PLoS One. 7:e533582012. View Article : Google Scholar : PubMed/NCBI
41.	Lan ML, Acharya MM, Tran KK, et al: Characterizing the radio-response of pluripotent and multipotent human stem cells. PLoS One. 7:e500482012. View Article : Google Scholar : PubMed/NCBI