microRNA-222 promotes tumor growth and confers radioresistance in nasopharyngeal carcinoma by targeting PTEN

Wu,Wei; Chen,Xi; Yu,Shilong; Wang,Rui; Zhao,Ruikun; Du,Chao

doi:10.3892/mmr.2017.7931

microRNA-222 promotes tumor growth and confers radioresistance in nasopharyngeal carcinoma by targeting PTEN

Authors:
- Wei Wu
- Xi Chen
- Shilong Yu
- Rui Wang
- Ruikun Zhao
- Chao Du
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Affiliations: Department of Radiation Oncology, Tumor Hospital of Jilin Province, Changchun, Jilin 130012, P.R. China, Department of Intervention, Tumor Hospital of Jilin Province, Changchun, Jilin 130012, P.R. China, Department of Radiation, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Neurosurgery, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: October 31, 2017 https://doi.org/10.3892/mmr.2017.7931
Pages: 1305-1310

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Abstract

MicroRNA-222 (miR‑222) has been reported to be involved in the initiation, development and metastasis of tumors, as well as conferring resistance to chemotherapeutic drugs or radiotherapy in various types of cancer. However, the role and the underlying molecular mechanism of miR‑222 specifically in nasopharyngeal carcinoma (NPC) remains unclear. Thus, the biological function and underlying mechanism of in miR‑222 was investigated in NPC tissue specimens and cell lines. miR‑222 was upregulated in NPC tissues and malignant cell lines compared with adjacent normal samples and cell lines. miR‑222 upregulation significantly increased NPC cell proliferation, colony formation and cell apoptosis. Furthermore, miR‑222 upregulation conferred radioresistance. It was also confirmed that phosphatase and tensin homolog (PTEN) was a direct target for miR‑222 in NPC cells. Alteration of miR‑222 expression was demonstrated to regulate the phosphoinositide 3‑kinase/protein kinase B pathway in NPC cells. These results suggest that miR‑222 may act as an oncomir in NPC by targeting PTEN, and has potential as a therapeutic target in NPC.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Lai SZ, Li WF, Chen L, Luo W, Chen YY, Liu LZ, Sun Y, Lin AH, Liu MZ and Ma J: How does intensity-modulated radiotherapy versus conventional two-dimensional radiotherapy influence the treatment results in nasopharyngeal carcinoma patients? Int J Radiat Oncol Biol Phys. 80:661–668. 2011. View Article : Google Scholar : PubMed/NCBI
3	Xiao WW, Huang SM, Han F, Wu SX, Lu LX, Lin CG, Deng XW, Lu TX, Cui NJ and Zhao C: Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy: Long-term results of a phase 2 study. Cancer. 117:1874–1883. 2011. View Article : Google Scholar : PubMed/NCBI
4	Brennecke J and Cohen SM: Towards a complete description of the microRNA complement of animal genomes. Genome Biol. 4:2282003. View Article : Google Scholar : PubMed/NCBI
5	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
6	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
7	Carthew RW and Sontheimer EJ: Origins and Mechanisms of miRNAs and siRNAs. Cell. 136:642–655. 2009. View Article : Google Scholar : PubMed/NCBI
8	Esquela-Kerscher A and Slack FJ: Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
9	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
10	Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:2257–2261. 2006. View Article : Google Scholar : PubMed/NCBI
11	Kang M, Xiao J, Wang J, Zhou P, Wei T, Zhao T and Wang R: MiR-24 enhances radiosensitivity in nasopharyngeal carcinoma by targeting SP1. Cancer Med. 5:1163–1173. 2016. View Article : Google Scholar : PubMed/NCBI
12	Lin T, Zhou F, Zhou H, Pan X, Sun Z and Peng G: MicroRNA-378g enhanced radiosensitivity of NPC cells partially by targeting protein tyrosine phosphatase SHP-1. Int J Radiat Biol. 91:859–866. 2015. View Article : Google Scholar : PubMed/NCBI
13	Zhao L, Tang M, Hu Z, Yan B, Pi W, Li Z, Zhang J, Zhang L, Jiang W, Li G, et al: miR-504 mediated down-regulation of nuclear respiratory factor 1 leads to radio-resistance in nasopharyngeal carcinoma. Oncotarget. 6:15995–16018. 2015. View Article : Google Scholar : PubMed/NCBI
14	Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S and Majumder S: MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1. J Biol Chem. 283:29897–29903. 2008. View Article : Google Scholar : PubMed/NCBI
15	Rao X, Di Leva G, Li M, Fang F, Devlin C, Hartman-Frey C, Burow ME, Ivan M, Croce CM and Nephew KP: MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene. 30:1082–1097. 2011. View Article : Google Scholar : PubMed/NCBI
16	Lee JC, Zhao JT, Clifton-Bligh RJ, Gill A, Gundara JS, Ip JC, Glover A, Sywak MS, Delbridge LW, Robinson BG and Sidhu SB: MicroRNA-222 and microRNA-146b are tissue and circulating biomarkers of recurrent papillary thyroid cancer. Cancer. 119:4358–4365. 2013. View Article : Google Scholar : PubMed/NCBI
17	Li W, Guo F, Wang P, Hong S and Zhang C: miR-221/222 confers radioresistance in glioblastoma cells through activating AKT independent of PTEN status. Curr Mol Med. 14:185–195. 2014. View Article : Google Scholar : PubMed/NCBI
18	Chun-Zhi Z, Lei H, An-Ling Z, Yan-Chao F, Xiao Y, Guang-Xiu W, Zhi-Fan J, Pei-Yu P, Qing-Yu Z and Chun-Sheng K: MicroRNA-221 and microRNA-222 regulate gastric carcinoma cell proliferation and radioresistance by targeting PTEN. BMC Cancer. 10:3672010. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Yamada KM and Araki M: Tumor suppressor PTEN: Modulator of cell signaling, growth, migration and apoptosis. J Cell Sci. 114:2375–2382. 2001.PubMed/NCBI
21	Wang Y, Guo Z, Shu Y, Zhou H, Wang H and Zhang W: BART miRNAs: An unimaginable force in the development of nasopharyngeal carcinoma. Eur J Cancer Prev. 26:144–150. 2017. View Article : Google Scholar : PubMed/NCBI
22	Yamashita R, Sato M, Kakumu T, Hase T, Yogo N, Maruyama E, Sekido Y, Kondo M and Hasegawa Y: Growth inhibitory effects of miR-221 and miR-222 in non-small cell lung cancer cells. Cancer Med. 4:551–564. 2015. View Article : Google Scholar : PubMed/NCBI
23	Zhang DQ, Zhou CK, Jiang XW, Chen J and Shi BK: Increased expression of miR-222 is associated with poor prognosis in bladder cancer. World J Surg Oncol. 12:2412014. View Article : Google Scholar : PubMed/NCBI
24	Hwang MS, Yu N, Stinson SY, Yue P, Newman RJ, Allan BB and Dornan D: miR-221/222 targets adiponectin receptor 1 to promote the epithelial-to-mesenchymal transition in breast cancer. PLoS One. 8:e665022013. View Article : Google Scholar : PubMed/NCBI
25	Quintavalle C, Garofalo M, Zanca C, Romano G, Iaboni M, del Basso De Caro M, Martinez-Montero JC, Incoronato M, Nuovo G, Croce CM and Condorelli G: miR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPu. Oncogene. 31:858–868. 2012. View Article : Google Scholar : PubMed/NCBI
26	Wong QW, Ching AK, Chan AW, Choy KW, To KF, Lai PB and Wong N: MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling. Clin Cancer Res. 16:867–875. 2010. View Article : Google Scholar : PubMed/NCBI
27	Zhang S and Yu D: PI(3)king apart PTEN's role in cancer. Clin Cancer Res. 16:4325–4330. 2010. View Article : Google Scholar : PubMed/NCBI
28	Cai LM, Lyu XM, Luo WR, Cui XF, Ye YF, Yuan CC, Peng QX, Wu DH, Liu TF, Wang E, et al: EBV-miR-BART7-3p promotes the EMT and metastasis of nasopharyngeal carcinoma cells by suppressing the tumor suppressor PTEN. Oncogene. 34:2156–2166. 2015. View Article : Google Scholar : PubMed/NCBI
29	Zhou XM, Sun R, Luo DH, Sun J, Zhang MY, Wang MH, Yang Y, Wang HY and Mai SJ: Upregulated TRIM29 promotes proliferation and metastasis of nasopharyngeal carcinoma via PTEN/AKT/mTOR signal pathway. Oncotarget. 7:13634–13650. 2016. View Article : Google Scholar : PubMed/NCBI
30	Hafsi S, Pezzino FM, Candido S, Ligresti G, Spandidos DA, Soua Z, McCubrey JA, Travali S and Libra M: Gene alterations in the PI3K/PTEN/AKT pathway as a mechanism of drug-resistance (review). Int J Oncol. 40:639–644. 2012.PubMed/NCBI