MicroRNA-223 functions as an oncogene in human colorectal cancer cells

Zhang,Jufeng; Luo,Xia; Li,Huiming; Yue,Xupeng; Deng,Lin; Cui,Yuanyuan; Lu,Yanxin

doi:10.3892/or.2014.3173

MicroRNA-223 functions as an oncogene in human colorectal cancer cells

Authors:
- Jufeng Zhang
- Xia Luo
- Huiming Li
- Xupeng Yue
- Lin Deng
- Yuanyuan Cui
- Yanxin Lu
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Affiliations: School of Life Science and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China, College of Engineering, South China Agricultural University, Guangzhou, Guangdong 510642, P.R. China, Experimental Research Center, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China, Zhuhai Campus of Zunyi Medical College, Zhuhai, Guangdong 519041, P.R. China, Department of Urology, UC Davis Medical Center, Sacramento, CA, USA
Published online on: May 8, 2014 https://doi.org/10.3892/or.2014.3173
Pages: 115-120

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Abstract

Aberrant microRNA (miRNA) expression has been frequently observed in colorectal cancer (CRC), the third most common human cancer in the world. However, the roles of miRNAs in CRC remain poorly understood. The present study explored, identified and characterized the miRNAs that correlate with CRC progression. Deregulated level of microRNA-223 (miR-223) was screened out by miRNA microarray in colorectal tumor tissues and further confirmed by quantitative real-time PCR in a large cohort of CRC samples (n=90). After silencing miR-223 by artificial anti‑miR-223 (miR-223-inhibitor), WST-1 and colony formation assays were employed to assess cell proliferation, and cell migration and invasion were evaluated by wound healing test and Transwell assays, respectively. Compared with adjacent non-tumor tissues, 22 miRNAs were screened out in CRC tissues with significance (>2-fold), of which 13 were upregulated and 9 were downregulated. miR-223 is one of the noticeably upregulated miRNAs. Large cohort CRC sample analyses showed that a higher level of miR-223 correlated with a higher clinical stage. Reducing miR-223 expression resulted in a decreased cell proliferation, migration and invasion in CRC cells. miR-223 functions as an oncomiR in CRC, therefore serving as a potential diagnostic and therapeutic target for the treatment of CRC.

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1	Siegel R, Ward E, Brawley O and Jemal A: Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 61:212–236. 2011. View Article : Google Scholar : PubMed/NCBI
2	Center MM, Jemal A and Ward E: International trends in colorectal cancer incidence rates. Cancer Epidemiol Biomarkers Prev. 18:1688–1694. 2009. View Article : Google Scholar : PubMed/NCBI
3	Ferlay J, Shin HR, Bray F, Forman D, Mathers C and Parkin DM: Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 127:2893–2917. 2010. View Article : Google Scholar : PubMed/NCBI
4	Edwards BK, Ward E, Kohler BA, et al: Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 116:544–573. 2010.
5	Winter J, Jung S, Keller S, Gregory RI and Diederichs S: Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 11:228–234. 2009. 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	Qu J, Zhao L, Zhang P, et al: MicroRNA-195 chemosensitizes colon cancer cells to the chemotherapeutic drug doxorubicin by targeting the first binding site of BCL2L2 mRNA. J Cell Physiol. View Article : Google Scholar : 2013.[Epub ahead of print].
8	Catania A, Maira F, Skarmoutsou E, D’Amico F, Abounader R and Mazzarino MC: Insight into the role of microRNAs in brain tumors (Review). Int J Oncol. 40:605–624. 2012.PubMed/NCBI
9	Cherni I and Weiss GJ: miRNAs in lung cancer: large roles for small players. Future Oncol. 7:1045–1055. 2011. View Article : Google Scholar : PubMed/NCBI
10	Le Pennec S and Savagner F: MiRNAs in follicular thyroid tumors. Presse Med. 40:683–689. 2011.(In French).
11	Agostini M, Pucciarelli S, Calore F, Bedin C, Enzo M and Nitti D: miRNAs in colon and rectal cancer: a consensus for their true clinical value. Clin Chim Acta. 411:1181–1186. 2010. View Article : Google Scholar : PubMed/NCBI
12	Liu X, Zhang Z, Sun L, et al: microRNA-499-5p promotes cellular invasion and tumor metastasis in colorectal cancer by targeting FOXO4 and PDCD4. Carcinogenesis. 32:1798–1805. 2011. View Article : Google Scholar : PubMed/NCBI
13	He L and Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 5:522–531. 2004. View Article : Google Scholar : PubMed/NCBI
14	Croce CM: Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 10:704–714. 2009. View Article : Google Scholar : PubMed/NCBI
15	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
16	Corte H, Manceau G, Blons H and Laurent-Puig P: MicroRNA and colorectal cancer. Dig Liver Dis. 44:195–200. 2012. View Article : Google Scholar
17	Schetter AJ, Leung SY, Sohn JJ, et al: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 299:425–436. 2008. View Article : Google Scholar : PubMed/NCBI
18	Boni V, Zarate R, Villa JC, et al: Role of primary miRNA polymorphic variants in metastatic colon cancer patients treated with 5-fluorouracil and irinotecan. Pharmacogenomics J. 11:429–436. 2011. View Article : Google Scholar : PubMed/NCBI
19	Landi D, Gemignani F, Naccarati A, et al: Polymorphisms within micro-RNA-binding sites and risk of sporadic colorectal cancer. Carcinogenesis. 29:579–584. 2008. View Article : Google Scholar : PubMed/NCBI
20	Laios A, O’Toole S, Flavin R, et al: Potential role of miR-9 and miR-223 in recurrent ovarian cancer. Mol Cancer. 7:352008. View Article : Google Scholar : PubMed/NCBI
21	Gottardo F, Liu CG, Ferracin M, et al: Micro-RNA profiling in kidney and bladder cancers. Urol Oncol. 25:387–392. 2007. View Article : Google Scholar : PubMed/NCBI
22	Mathé EA, Nguyen GH, Bowman ED, et al: MicroRNA expression in squamous cell carcinoma and adenocarcinoma of the esophagus: associations with survival. Clin Cancer Res. 15:6192–6200. 2009.PubMed/NCBI
23	Li X, Zhang Y, Zhang H, et al: miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res. 9:824–833. 2011. View Article : Google Scholar : PubMed/NCBI
24	Kang W, Tong JH, Chan AW, et al: Stathmin1 plays oncogenic role and is a target of microRNA-223 in gastric cancer. PLoS One. 7:e339192012. View Article : Google Scholar : PubMed/NCBI
25	Mi S, Lu J, Sun M, et al: MicroRNA expression signatures accurately discriminate acute lymphoblastic leukemia from acute myeloid leukemia. Proc Natl Acad Sci USA. 104:19971–19976. 2007. View Article : Google Scholar : PubMed/NCBI
26	Miko E, Czimmerer Z, Csánky E, et al: Differentially expressed microRNAs in small cell lung cancer. Exp Lung Res. 35:646–664. 2009. View Article : Google Scholar : PubMed/NCBI
27	Karakatsanis A, Papaconstantinou I, Gazouli M, Lyberopoulou A, Polymeneas G and Voros D: Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance. Mol Carcinog. 52:297–303. 2013. View Article : Google Scholar
28	Wong QW, Lung RW, Law PT, et al: MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology. 135:257–269. 2008. View Article : Google Scholar : PubMed/NCBI
29	Sempere LF, Christensen M, Silahtaroglu A, et al: Altered MicroRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res. 67:11612–11620. 2007. View Article : Google Scholar : PubMed/NCBI
30	Xing J, Wan S, Zhou F, et al: Genetic polymorphisms in pre-microRNA genes as prognostic markers of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 21:217–227. 2012. View Article : Google Scholar : PubMed/NCBI
31	Lieberman DA: Clinical practice. Screening for colorectal cancer. N Engl J Med. 361:1179–1187. 2009. View Article : Google Scholar : PubMed/NCBI
32	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
33	Motoyama K, Inoue H, Takatsuno Y, et al: Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 34:1069–1075. 2009.PubMed/NCBI
34	Zhang J, Xiao Z, Lai D, et al: miR-21, miR-17 and miR-19a induced by phosphatase of regenerating liver-3 promote the proliferation and metastasis of colon cancer. Br J Cancer. 107:352–359. 2012. View Article : Google Scholar : PubMed/NCBI
35	Monzo M, Navarro A, Bandres E, et al: Overlapping expression of microRNAs in human embryonic colon and colorectal cancer. Cell Res. 18:823–833. 2008. View Article : Google Scholar : PubMed/NCBI
36	Liu H, Zhu L, Liu B, et al: Genome-wide microRNA profiles identify miR-378 as a serum biomarker for early detection of gastric cancer. Cancer Lett. 316:196–203. 2012. View Article : Google Scholar : PubMed/NCBI
37	Slaby O, Svoboda M, Fabian P, et al: Altered expression of miR-21, miR-31, miR-143 and miR-145 is related to clinicopathologic features of colorectal cancer. Oncology. 72:397–402. 2007. View Article : Google Scholar : PubMed/NCBI
38	Ng EK, Tsang WP, Ng SS, et al: MicroRNA-143 targets DNA methyltransferases 3A in colorectal cancer. Br J Cancer. 101:699–706. 2009. View Article : Google Scholar : PubMed/NCBI
39	Chen X, Guo X, Zhang H, et al: Role of miR-143 targeting KRAS in colorectal tumorigenesis. Oncogene. 28:1385–1392. 2009. View Article : Google Scholar : PubMed/NCBI