MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

Zhou,Hong‑Ping; Qian,Lu‑Xi; Zhang,Nan; Gu,Jia‑Jia; Ding,Kai; Wu,Jing; Lu,Zhi‑Wei; Du,Ming‑Yu; Zhu,Hong‑Ming; Wu,Jian‑Zhong; He,Xia; Yin,Li

doi:10.3892/ol.2018.8524

MIIP gene expression is associated with radiosensitivity in human nasopharyngeal carcinoma cells

Authors:
- Hong‑Ping Zhou
- Lu‑Xi Qian
- Nan Zhang
- Jia‑Jia Gu
- Kai Ding
- Jing Wu
- Zhi‑Wei Lu
- Ming‑Yu Du
- Hong‑Ming Zhu
- Jian‑Zhong Wu
- Xia He
- Li Yin
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Affiliations: The Fourth School of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China, Department of Radiation Oncology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, Jiangsu 210000, P.R. China, Department of Radiation Oncology, Suqian First Hospital, Suqian, Jiangsu 223800, P.R. China
Published online on: April 18, 2018 https://doi.org/10.3892/ol.2018.8524
Pages: 9471-9479

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Abstract

The present study aims to investigate the radiosensitization effect of the migration and invasion inhibitory protein (MIIP) gene on nasopharyngeal carcinoma (NPC) cells. The MIIP gene was transfected into NPC 5‑8F and CNE2 cells. The level of MIIP was analyzed by quantitative reverse transcription‑polymerase chain reaction analysis and western blot. The changes in radiosensitivity of the cells were analyzed by colony formation assay. The changes in cell apoptosis and cycle distribution following irradiation were detected by flow cytometry. The expression of BCL2 associated X, apoptosis regulator/B‑cell lymphoma 2 was evaluated using western blot. DNA damage was analyzed by counting γ‑H2AX foci. The expression levels of γ‑H2AX were evaluated by immunofluorescence and western blot. In a previous study by the authors, the results indicated that the expression of MIIP gene evidently increased in MIIP‑transfected 5‑8F (5‑8F OE) and MIIP‑transfected CNE2 (CNE2 OE) cells compared with the parental or negative control cells. In the present study, the survival rate of 5‑8F OE and CNE2 OE cells markedly decreased following irradiation (0, 2, 4, 6 and 8 Gy) compared with the negative control (5‑8F NC and CNE2 NC) and the untreated (5‑8F and CNE2) groups. The expression of MIIP was able to increase apoptosis, which resulted in G2/M cell cycle arrest and DNA damage repair was attenuated in 5‑8F and CNE2 cells following irradiation as measured by the accumulation of γ‑H2AX. It was indicated that MIIP expression is associated with the radiosensitivity of NPC cells and has a significant role in regulating cell radiosensitivity.

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1	Zhang L, Huang Y, Hong S, Yang Y, Yu G, Jia J, Peng P, Wu X, Lin Q, Xi X, et al: Gemcitabine plus cisplatin versus fluorouracil plus cisplatin in recurrent or metastatic nasopharyngeal carcinoma: A multicentre, randomised, open-label, phase 3 trial. Lancet. 388:1883–1892. 2016. View Article : Google Scholar : PubMed/NCBI
2	Wang S, Pan Y, Zhang R, Xu T, Wu W, Zhang R, Wang C, Huang H, Calin CA, Yang H and Claret FX: Hsa-miR-24-3p increases nasopharyngeal carcinoma radiosensitivity by targeting both the 3′UTR and 5′UTR of Jab1/CSN5. Oncogene. 35:6096–6108. 2016. View Article : Google Scholar : PubMed/NCBI
3	Song F, Zhang L, Ji P, Zheng H, Zhao Y, Zhang W and Chen K: Altered expression and loss of heterozygosity of the migration and invasion inhibitory protein (MIIP) gene in breast cancer. Oncol Rep. 33:2771–2778. 2015. View Article : Google Scholar : PubMed/NCBI
4	Wang Y, Hu L, Ji P, Teng F, Tian W, Liu Y, Cogdell D, Liu J, Sood AK, Broaddus R, et al: MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis. J Hematol Oncol. 9:1122016. View Article : Google Scholar : PubMed/NCBI
5	Wen J, Fu J, Ling Y and Zhang W: MIIP accelerates epidermal growth factor receptor protein turnover and attenuates proliferation in non-small cell lung cancer. Oncotarget. 7:9118–9134. 2016. View Article : Google Scholar : PubMed/NCBI
6	Song SW, Fuller GN, Khan A, Kong S, Shen W, Taylor E, Ramdas L, Lang FF and Zhang W: IIp45, an insulin-like growth factor binding protein 2 (IGFBP-2) binding protein, antagonizes IGFBP-2 stimulation of glioma cell invasion. Proc Natl Acad Sci USA. 100:13970–13975. 2003. View Article : Google Scholar : PubMed/NCBI
7	Song F, Ji P, Zheng H, Song F, Wang Y, Hao X, Wei Q, Zhang W and Chen K: Definition of a functional single nucleotide polymorphism in the cell migration inhibitory gene MIIP that affects the risk of breast cancer. Cancer Res. 70:1024–1032. 2010. View Article : Google Scholar : PubMed/NCBI
8	Gibbs M, Stanford JL, McIndoe RA, Jarvik GP, Kolb S, Goode EL, Chakrabarti L, Schuster EF, Buckley VA, Miller EL, et al: Evidence for a rare prostate cancer-susceptibility locus at chromosome 1p36. Am J Hum Genet. 64:776–787. 1999. View Article : Google Scholar : PubMed/NCBI
9	Choma MK, Lumb J, Kozik P and Robinson MS: A genome-wide screen for machinery involved in downregulation of MHC class I by HIV-1 Nef. PLoS One. 10:e01404042015. View Article : Google Scholar : PubMed/NCBI
10	Fujita T, Igarashi J, Okawa ER, Gotoh T, Manne J, Kolla V, Kim J, Zhao H, Pawel BR, London WB, et al: CHD5, a tumor suppressor gene deleted from 1p36.31 in neuroblastomas. J Natl Cancer Institute. 100:940–949. 2008. View Article : Google Scholar
11	Shao JY, Wang HY, Huang XM, Feng QS, Huang P, Feng BJ, Huang LX, Yu XJ, Li JT, Hu LF, et al: Genome-wide allelotype analysis of sporadic primary nasopharyngeal carcinoma from southern China. Int J Oncol. 17:1267–1275. 2000.PubMed/NCBI
12	Huang B, Zhang L, Yan J, Liang Q and Fang Y: Fine mapping of the loss of heterozygosity for chromosome 1pter-p36.11 in nasopharyngeal carcinoma. Zhonghua Bing Li Xue Za Zhi. 30:110–113. 2001.(In Chinese). PubMed/NCBI
13	Shao JY, Huang XM, Yu XJ, Huang LX, Wu QL, Xia JC, Wang HY, Feng QS, Ren ZF, Ernberg I, et al: Loss of heterozygosity and its correlation with clinical outcome and Epstein-Barr virus infection in nasopharyngeal carcinoma. Anticancer Res. 21:3021–3029. 2001.PubMed/NCBI
14	Rogakou EP, Pilch DR, Orr AH, Ivanova VS and Bonner WM: DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem. 273:5858–5868. 1998. View Article : Google Scholar : PubMed/NCBI
15	Downs JA, Lowndes NF and Jackson SP: A role for Saccharomyces cerevisiae histone H2A in DNA repair. Nature. 408:1001–1004. 2000. View Article : Google Scholar : PubMed/NCBI
16	Foster ER and Downs JA: Histone H2A phosphorylation in DNA double-strand break repair. FEBS J. 272:3231–3240. 2005. View Article : Google Scholar : PubMed/NCBI
17	Celeste A, Difilippantonio S, Difilippantonio MJ, Fernandez-Capetillo O, Pilch DR, Sedelnikova OA, Eckhaus M, Ried T, Bonner WM and Nussenzweig A: H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell. 114:371–383. 2003. View Article : Google Scholar : PubMed/NCBI
18	Berkovich E, Monnat RJ Jr and Kastan MB: Roles of ATM and NBS1 in chromatin structure modulation and DNA double-strand break repair. Nat Cell Biol. 9:683–690. 2007. View Article : Google Scholar : PubMed/NCBI
19	Strong MJ, Baddoo M, Nanbo A, Xu M, Puetter A and Lin Z: Comprehensive high-throughput RNA sequencing analysis reveals contamination of multiple nasopharyngeal carcinoma cell lines with HeLa cell genomes. J Virol. 88:10696–10704. 2014. View Article : Google Scholar : PubMed/NCBI
20	Tan Y, Guo Q, Xie Q, Wang K, Yuan B, Zhou Y, Liu J, Huang J, He X, Yang X, et al: Single-walled carbon nanotubes (SWCNTs)-assisted cell-systematic evolution of ligands by exponential enrichment (cell-SELEX) for improving screening efficiency. Anal Chem. 86:9466–9472. 2014. View Article : Google Scholar : PubMed/NCBI
21	Liu T, Sun Q, Li Q, Yang H, Zhang Y, Wang R, Lin X, Xiao D, Yuan Y, Chen L and Wang W: Dual PI3K/mTOR inhibitors, GSK2126458 and PKI-587, suppress tumor progression and increase radiosensitivity in nasopharyngeal carcinoma. Mol Cancer Ther. 14:429–439. 2015. View Article : Google Scholar : PubMed/NCBI
22	Zhou Z, Zhang L, Xie B, Wang X, Yang X, Ding N, Zhang J, Liu Q, Tan G, Feng D and Sun LQ: FOXC2 promotes chemoresistance in nasopharyngeal carcinomas via induction of epithelial mesenchymal transition. Cancer Lett. 363:137–145. 2015. View Article : Google Scholar : PubMed/NCBI
23	Kuang CM, Fu X, Hua YJ, Shuai WD, Ye ZH, Li Y, Peng QH, Li YZ, Chen S, Qian CN, et al: BST2 confers cisplatin resistance via NF-kappaB signaling in nasopharyngeal cancer. Cell Death Dis. 8:e28742017. View Article : Google Scholar : PubMed/NCBI
24	Kawamura K, Qi F and Kobayashi J: Potential relationship between the biological effects of low-dose irradiation and mitochondrial ROS production. J Radiat Res. Feb 3–2018.Doi: 10.1093/jrr/rrx091. View Article : Google Scholar : PubMed/NCBI
25	Yuan L, Yi HM, Yi H, Qu JQ, Zhu JF, Li LN, Xiao T, Zheng Z, Lu SS and Xiao ZQ: Reduced RKIP enhances nasopharyngeal carcinoma radioresistance by increasing ERK and AKT activity. Oncotarget. 7:11463–11477. 2016.PubMed/NCBI
26	Chistiakov DA, Voronova NV and Chistiakov PA: Genetic variations in DNA repair genes, radiosensitivity to cancer and susceptibility to acute tissue reactions in radiotherapy-treated cancer patients. Acta Oncol. 47:809–824. 2008. View Article : Google Scholar : PubMed/NCBI
27	Zhang Z, Lang J, Cao Z, Li R, Wang X and Wang W: Radiation-induced SOD2 overexpression sensitizes colorectal cancer to radiation while protecting normal tissue. Oncotarget. 8:7791–7800. 2017.PubMed/NCBI
28	Liu ZG, Jiang G, Tang J, Wang H, Feng G, Chen F, Tu Z, Liu G, Zhao Y, Peng MJ, et al: c-Fos over-expression promotes radioresistance and predicts poor prognosis in malignant glioma. Oncotarget. 7:65946–65956. 2016.PubMed/NCBI
29	Tewari D, Monk BJ, Al-Ghazi MS, Parker R, Heck JD, Burger RA and Fruehauf JP: Gene expression profiling of in vitro radiation resistance in cervical carcinoma: A feasibility study. Gynecol Oncol. 99:84–91. 2005. View Article : Google Scholar : PubMed/NCBI
30	Harima Y, Togashi A, Horikoshi K, Imamura M, Sougawa M, Sawada S, Tsunoda T, Nakamura Y and Katagiri T: Prediction of outcome of advanced cervical cancer to thermoradiotherapy according to expression profiles of 35 genes selected by cDNA microarray analysis. Int J Radiat Oncol Biol Phys. 60:237–248. 2004. View Article : Google Scholar : PubMed/NCBI
31	Cengel KA, Voong KR, Chandrasekaran S, Maggiorella L, Brunner TB, Stanbridge E, Kao GD, McKenna WG and Bernhard EJ: Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells. Neoplasia. 9:341–348. 2007. View Article : Google Scholar : PubMed/NCBI
32	Langland GT, Yannone SM, Langland RA, Nakao A, Guan Y, Long SB, Vonguyen L, Chen DJ, Gray JW and Chen F: Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities. Oncol Rep. 23:1021–1026. 2010. View Article : Google Scholar : PubMed/NCBI
33	Huang EY, Chen YF, Chen YM, Lin IH, Wang CC, Su WH, Chuang PC and Yang KD: A novel radioresistant mechanism of galectin-1 mediated by H-Ras-dependent pathways in cervical cancer cells. Cell Death Dis. 3:e2512012. View Article : Google Scholar : PubMed/NCBI
34	Wang Y, Wen J and Zhang W: MIIP, a cytoskeleton regulator that blocks cell migration and invasion, delays mitosis, and suppresses tumorogenesis. Curr Protein Pept Sci. 12:68–73. 2011. View Article : Google Scholar : PubMed/NCBI
35	Nahas SA and Gatti RA: DNA double strand break repair defects, primary immunodeficiency disorders, and ‘radiosensitivity’. Curr Opin Allergy Clin Immunol. 9:510–516. 2009. View Article : Google Scholar : PubMed/NCBI
36	Selzer E and Hebar A: Basic principles of molecular effects of irradiation. Wien Med Wochenschr. 162:47–54. 2012. View Article : Google Scholar : PubMed/NCBI
37	Williams JR, Zhang Y, Zhou H, Russell J, Gridley DS, Koch CJ and Little JB: Genotype-dependent radiosensitivity: Clonogenic survival, apoptosis and cell-cycle redistribution. Int J Radiat Biol. 84:151–164. 2008. View Article : Google Scholar : PubMed/NCBI
38	Brentnall M, Rodriguez-Menocal L, De Guevara RL, Cepero E and Boise LH: Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 14:322013. View Article : Google Scholar : PubMed/NCBI
39	Martinou JC and Youle RJ: Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 21:92–101. 2011. View Article : Google Scholar : PubMed/NCBI
40	Selvarajah J, Elia A, Carroll VA and Moumen A: DNA damage-induced S and G2/M cell cycle arrest requires mTORC2-dependent regulation of Chk1. Oncotarget. 6:427–440. 2015. View Article : Google Scholar : PubMed/NCBI
41	Kastan MB and Bartek J: Cell-cycle checkpoints and cancer. Nature. 432:316–323. 2004. View Article : Google Scholar : PubMed/NCBI
42	Toyoshima M: Analysis of p53 dependent damage response in sperm-irradiated mouse embryos. J Radiat Res. 50:11–17. 2009. View Article : Google Scholar : PubMed/NCBI
43	Hiro J, Inoue Y, Toiyama Y, Yoshiyama S, Tanaka K, Mohri Y, Miki C and Kusunoki M: Possibility of paclitaxel as an alternative radiosensitizer to 5-fluorouracil for colon cancer. Oncol Rep. 24:1029–1034. 2010.PubMed/NCBI
44	Zheng L, Tang W, Wei F, Wang H, Liu J, Lu Y, Cheng Y, Bai X, Yu X and Zhao W: Radiation-inducible protein RbAp48 contributes to radiosensitivity of cervical cancer cells. Gynecol Oncol. 130:601–608. 2013. View Article : Google Scholar : PubMed/NCBI
45	Bartek J, Bartkova J and Lukas J: DNA damage signalling guards against activated oncogenes and tumour progression. Oncogene. 26:7773–7779. 2007. View Article : Google Scholar : PubMed/NCBI
46	Bartek J and Lukas J: DNA damage checkpoints: From initiation to recovery or adaptation. Curr Opin Cell Biol. 19:238–245. 2007. View Article : Google Scholar : PubMed/NCBI
47	van Attikum H, Fritsch O, Hohn B and Gasser SM: Recruitment of the INO80 complex by H2A phosphorylation links ATP-dependent chromatin remodeling with DNA double-strand break repair. Cell. 119:777–788. 2004. View Article : Google Scholar : PubMed/NCBI
48	Park JH, Park EJ, Lee HS, Kim SJ, Hur SK, Imbalzano AN and Kwon J: Mammalian SWI/SNF complexes facilitate DNA double-strand break repair by promoting gamma-H2AX induction. EMBO J. 25:3986–3997. 2006. View Article : Google Scholar : PubMed/NCBI
49	Kobayashi J, Fujimoto H, Sato J, Hayashi I, Burma S, Matsuura S, Chen DJ and Komatsu K: Nucleolin participates in DNA double-strand break-induced damage response through MDC1-dependent pathway. PLoS One. 7:e492452012. View Article : Google Scholar : PubMed/NCBI