5-Fluorouracil in combination with cisplatin alters the microRNA expression profile in the CNE nasopharyngeal carcinoma cell line

Zhang,Xuebang; Li,Wenfeng

doi:10.3892/mmr.2012.917

5-Fluorouracil in combination with cisplatin alters the microRNA expression profile in the CNE nasopharyngeal carcinoma cell line

Authors:
- Xuebang Zhang
- Wenfeng Li
View Affiliations

Affiliations: Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China
Published online on: May 16, 2012 https://doi.org/10.3892/mmr.2012.917
Pages: 303-308

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chemotherapy constitutes one of the chief supplementary methods in the treatment of nasopharyngeal carcinoma (NPC). 5-Fluorouracil (5-FU) and cisplatin are classic chemotherapeutic drugs that have been widely used for NPC treatment. Although the aberrant expression of protein-coding genes has been observed after chemotherapy, the regulatory mechanisms involved remain poorly understood. MicroRNAs (miRNAs) are a newly identified class of small regulatory RNAs involved in multiple biological processes and metabolic regulation, including the initiation, progression and metastasis of human cancers. In this study, using a label-free high-throughput microRNA array technology, the stacking-hybridized universal tag (SHUT) assay, we show that 5-FU in combination with cisplatin significantly alters the global expression profile of miRNAs in CNE cells. After 48 h of treatment with a low dose [10% inhibitory concentration (IC10)] of 5-FU and/or cisplatin, numerous key miRNAs were shown to be regulated. Compared to the 431 miRNAs detected in the control cells, 184 miRNAs were significantly expressed in the 5-FU-treated cells, while 336 miRNAs were expressed in the cisplatin-treated cells and 13 miRNAs in the cells treated with the combination of both drugs. The majority of these miRNAs are associated with cancer development, progression and metastasis. This is the first time that miRNA expression profiles in the CNE cell line are shown. Our findings elucidate a potential mechanism involved in the chemotherapy of NPC and provide new clues for the treatment of NPC.

View Figures

View References

1	Brennan B: Nasopharyngeal carcinoma. Orphanet J Rare Dis. 1:232006.
2	Chang ET and Adami HO: The enigmatic epidemiology of nasopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 15:1765–1777. 2006.
3	Fang W, Li X, Jiang Q, et al: Transcriptional patterns, biomarkers and pathways characterizing nasopharyngeal carcinoma of Southern China. J Transl Med. 6:322008.
4	Young JL Jr and Miller RW: Incidence of malignant tumors in U.S. Children. J Pediatr. 86:254–258. 1975.
5	Joensuu H: Systemic chemotherapy for cancer: from weapon to treatment. Lancet Oncol. 9:3042008.
6	Al-Sarraf M: Head and neck cancer: chemotherapy concepts. Semin Oncol. 15:70–85. 1988.
7	Jacobs C, Lyman G, Velez-García E, Sridhar KS, Knight W, Hochster H, Goodnough LT, Mortimer JE, Einhorn LH, et al: A phase III randomized study comparing cisplatin and fluorouracil as single agents and in combination for advanced squamous cell carcinoma of the head and neck. J Clin Oncol. 10:257–263. 1992.
8	Foo KF, Tan EH, Leong SS, Wee JT, Tan T, Fong KW, Koh L, Tai BC, Lian LG and Machin D: Gemcitabine in metastatic nasopharyngeal carcinoma of the undifferentiated type. Ann Oncol. 13:150–156. 2002.
9	Rosenberg B, Vancamp L, Trosko JE and Mansour VH: Platinum compounds: a new class of potent antitumour agents. Nature. 222:385–386. 1969.
10	Heidelberger C, Chaudhuri NK, Danneberg P, et al: Fluorinated pyrimidines, a new class of tumour-inhibitory compounds. Nature. 179:663–666. 1957.
11	Santi DV, McHenry CS and Sommer H: Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry. 13:471–481. 1974.
12	Sommer H and Santi DV: Purification and amino acid analysis of an active site peptide from thymidylate synthetase containing covalently bound 5-fluoro-20-deoxyuridylate and methylenetetrahydrofolate. Biochem Biophys Res Commun. 57:689–695. 1974.
13	Maxwell PJ, Longley DB, Latif T, et al: Identification of 5-fluorouracil-inducible target genes using cDNA microarray profiling. Cancer Res. 63:4602–4606. 2003.
14	Mauritz R, van Groeningen CJ, Smid K, et al: Thymidylate synthase and dihydropyrimidine dehydrogenase mRNA expression after administration of 5-fluorouracil to patients with colorectal cancer. Int J Cancer. 120:2609–2612. 2007.
15	Shah MY, Pan X, Fix LN, Farwell MA and Zhang B: 5-Fluorouracil drug alters the microRNA expression profiles in MCF-7 breast cancer cells. J Cell Physiol. 226:1868–1878. 2011.
16	Zhang BH, Pan XP, Cobb GP and Anderson TA: microRNAs as oncogenes and tumor suppressors. Dev Biol. 302:1–12. 2007.
17	Zhang BH, Stellwag EJ and Pan XP: Large-scale genome analysis reveals unique features of microRNAs. Gene. 443:100–109. 2009.
18	Koturbash I, Zemp FJ, Pogribny I and Kovalchuk O: Small molecules with big effects: the role of the microRNAome in cancer and Carcinogenesis. Mutat Res. 722:94–105. 2011.
19	Meng F, Henson R, Lang M, et al: Involvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell lines. Gastroenterology. 130:2113–2129. 2006.
20	Xia L, Zhang D, Du R, et al: miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 123:372–379. 2008.
21	Kovalchuk O, Filkowski J, Meservy J, et al: Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther. 7:2152–2159. 2008.
22	Rossi L, Bonmassar E and Faraoni I: Modification of miR gene expression pattern in human colon cancer cells following exposure to 5-fluorouracil in vitro. Pharmacol Res. 56:248–253. 2007.
23	Duan D, Zheng KX, Shen Y, et al: Label-free high-throughput microRNA expression profiling from total RNA. Nucleic Acids Res. 39:e1542011.
24	Park SY, Lee JH, Ha M, et al: miR-29 miRNAs activate p53 by targeting p85 alpha and CDC42. Nat Struct Mol Biol. 16:23–29. 2009.
25	Reina Ortiz M, Schreiber F, Benitez S, et al: Effects of chronic ascariasis and trichuriasis on cytokine production and gene expression in human blood: a cross-sectional study. PLoS Neql Trop Dis. 5:e11572011.
26	Xie YF, Shu R, Jiang SY, et al: Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues. Int J Oral Sci. 3:125–134. 2011.
27	Tian RQ, Wang XH, Hou LJ, et al: MicroRNA-372 is down-regulated and targets cyclin-dependent kinase 2 (CDK2) and cyclin A1 in human cervical cancer, which may contribute to tumorigenesis. J Biol Chem. 286:25556–25563. 2011.