Downregulation of microRNA-21 enhances radiosensitivity in nasopharyngeal carcinoma

Zhu,Honghai; Zhu,Xiaoyuan; Cheng,Genyang; Zhou,Minghui; Lou,Weihua

doi:10.3892/etm.2015.2403

Downregulation of microRNA-21 enhances radiosensitivity in nasopharyngeal carcinoma

Authors:
- Honghai Zhu
- Xiaoyuan Zhu
- Genyang Cheng
- Minghui Zhou
- Weihua Lou
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Affiliations: Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: April 2, 2015 https://doi.org/10.3892/etm.2015.2403
Pages: 2185-2189

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Abstract

Radioresistance severely restricts the clinical treatment of nasopharyngeal carcinoma (NPC). microRNAs (miRs) have been demonstrated to affect cancer progression and radiosensitivity. Thus, the aim of the present study was to identify miRs associated with radioresistance in NPC. A radioresistant NPC cell line (CNE‑2‑1) was established by continuously exposing CNE‑2 cells to radiation. Subsequently, high‑throughput sequencing technology was used to detect the regulation of miRs in radioresistant CNE‑2‑1 cells, and it was observed that miR-21 was among the three most upregulated miRs in CNE-2-1 cells. Therefore, the expression levels of miR‑21 were quantified using reverse transcription‑quantitative polymerase chain reaction. Finally, the function of miR‑21 was investigated by downregulating the expression in the CNE‑2‑1 cells. The results indicated that the expression of miR‑21 was significantly increased in the CNE‑2‑1 cells, as compared with the CNE‑2 cells. In addition, downregulation of miR‑21 resulted in enhanced radiosensitivity in the CNE‑2‑1 cells, as demonstrated by the inhibition in cell viability of these radioresistant cells. Further analysis indicated that miR‑21 was able to inhibit the proliferation of CNE‑2‑1 cells at the G1 phase of the cell cycle. Therefore, these results indicated that miR‑21 was able to regulate radioresistance in NPC cells; however, further studies are required to confirm this hypothesis.

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1	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
2	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
3	He H, Jazdzewski K, Li W, et al: The role of microRNA genes in papillary thyroid carcinoma. Proc Natl Acad Sci USA. 102:19075–19080. 2005. View Article : Google Scholar : PubMed/NCBI
4	Voorhoeve PM, le Sage C, Schrier M, et al: A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell. 124:1169–1181. 2006. View Article : Google Scholar : PubMed/NCBI
5	Wu L, Fan J and Belasco JG: MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci USA. 103:4034–4039. 2006. View Article : Google Scholar : PubMed/NCBI
6	Wei WI and Sham JS: Nasopharyngeal carcinoma. Lancet. 365:2041–2054. 2005. View Article : Google Scholar : PubMed/NCBI
7	Lin J-C: Adjuvant chemotherapy in advanced nasopharyngeal carcinoma based on plasma EBV load. J Radiat Oncol. 1:117–127. 2012. View Article : Google Scholar
8	Li T, Chen JX, Fu XP, et al: microRNA expression profiling of nasopharyngeal carcinoma. Oncol Rep. 25:1353–1363. 2011.PubMed/NCBI
9	Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2009. CA Cancer J Clin. 59:225–249. 2009. View Article : Google Scholar : PubMed/NCBI
10	Zhang L, Deng T, Li X, et al: microRNA-141 is involved in a nasopharyngeal carcinoma-related genes network. Carcinogenesis. 31:559–566. 2010. View Article : Google Scholar : PubMed/NCBI
11	Xia H, Ng SS, Jiang S, et al: miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion. Biochem Biophys Res Commun. 391:535–541. 2010. View Article : Google Scholar : PubMed/NCBI
12	Wong TS, Man OY, Tsang CM, et al: MicroRNA let-7 suppresses nasopharyngeal carcinoma cells proliferation through downregulating c-Myc expression. J Cancer Res Clin Oncol. 137:415–422. 2011. View Article : Google Scholar : PubMed/NCBI
13	Shi W, Alajez NM, Bastianutto C, et al: Significance of Plk1 regulation by miR-100 in human nasopharyngeal cancer. Int J Cancer. 126:2036–2048. 2010.PubMed/NCBI
14	Chen C, Ridzon DA, Broomer AJ, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
15	Calin GA, Sevignani C, Dumitru CD, et al: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA. 101:2999–3004. 2004. View Article : Google Scholar : PubMed/NCBI
16	Sevignani C, Calin GA, Nnadi SC, et al: MicroRNA genes are frequently located near mouse cancer susceptibility loci. Proc Natl Acad Sci USA. 104:8017–8022. 2007. View Article : Google Scholar : PubMed/NCBI
17	Fåhraeus R, Fu HL, Ernberg I, et al: Expression of Epstein-Barr virus-encoded proteins in nasopharyngeal carcinoma. Int J Cancer. 42:329–338. 1988. View Article : Google Scholar : PubMed/NCBI
18	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI
19	Sun K and Lai EC: Adult-specific functions of animal microRNAs. Nat Rev Genet. 14:535–548. 2013. View Article : Google Scholar : PubMed/NCBI
20	Ameres SL and Zamore PD: Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 14:475–488. 2013. View Article : Google Scholar : PubMed/NCBI
21	van Kouwenhove M, Kedde M and Agami R: MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 11:644–656. 2011. View Article : Google Scholar : PubMed/NCBI
22	Kasinski AL and Slack FJ: Epigenetics and genetics. MicroRNAs en route to the clinic: Progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 11:849–864. 2011. View Article : Google Scholar : PubMed/NCBI
23	Iorio MV and Croce CM: MicroRNA dysregulation in cancer: Diagnostics, monitoring and therapeutics. A comprehensive review. EMBO Mol Med. 4:143–159. 2012. View Article : Google Scholar : PubMed/NCBI
24	Valencia-Sanchez MA, Liu J, Hannon GJ and Parker R: Control of translation and mRNA degradation by miRNAs and siRNAs. Gene Dev. 20:515–524. 2006. View Article : Google Scholar : PubMed/NCBI
25	Chen HC, Chen GH, Chen YH, et al: MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma. Br J Cancer. 100:1002–1011. 2009. View Article : Google Scholar : PubMed/NCBI
26	Liu Y, Li Z, Wu L, et al: MiRNA-125a-5p: A regulator and predictor of gefitinib's effect on nasopharyngeal carcinoma. Cancer Cell Int. 14:242014. View Article : Google Scholar : PubMed/NCBI
27	Li G, Liu Y, Su Z, et al: MicroRNA-324-3p regulates nasopharyngeal carcinoma radioresistance by directly targeting WNT2B. Eur J Cancer. 49:2596–2607. 2013. View Article : Google Scholar : PubMed/NCBI
28	Lu J, Getz G, Miska EA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
29	Deng M, Gu Y, Zheng G, et al: Expression and clinical significance of miR-21 in nasopharyngeal carcinoma. Shandong Med J. 52:10–12. 2012.