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http://dx.doi.org/10.14348/molcells.2014.0151

A Long Non-Coding RNA snaR Contributes to 5-Fluorouracil Resistance in Human Colon Cancer Cells  

Lee, Heejin (Department of Biochemistry, College of Medicine, Catholic University of Korea)
Kim, Chongtae (Department of Biochemistry, College of Medicine, Catholic University of Korea)
Ku, Ja-Lok (Cancer Research Institute and Cancer Research Center, Seoul National University)
Kim, Wook (Department of Molecular Science and Technology, Ajou University)
Kim Yoon, Sungjoo (Cancer Evolution Research Center, College of Medicine, Catholic University of Korea)
Kuh, Hyo-Jeong (Cancer Evolution Research Center, College of Medicine, Catholic University of Korea)
Lee, Jeong-Hwa (Department of Biochemistry, College of Medicine, Catholic University of Korea)
Nam, Suk Woo (Cancer Evolution Research Center, College of Medicine, Catholic University of Korea)
Lee, Eun Kyung (Department of Biochemistry, College of Medicine, Catholic University of Korea)
Abstract
Several types of genetic and epigenetic regulation have been implicated in the development of drug resistance, one significant challenge for cancer therapy. Although changes in the expression of non-coding RNA are also responsible for drug resistance, the specific identities and roles of them remain to be elucidated. Long non-coding RNAs (lncRNAs) are a type of ncRNA (> 200 nt) that influence the regulation of gene expression in various ways. In this study, we aimed to identify differentially expressed lncRNAs in 5-fluorouracil-resistant colon cancer cells. Using two pairs of 5-FU-resistant cells derived from the human colon cancer cell lines SNU-C4 and SNU-C5, we analyzed the expression of 90 lncRNAs by qPCR-based profiling and found that 19 and 23 lncRNAs were differentially expressed in SNU-C4R and SNU-C5R cells, respectively. We confirmed that snaR and BACE1AS were down-regulated in resistant cells. To further investigate the effects of snaR on cell growth, cell viability and cell cycle were analyzed after transfection of siRNAs targeting snaR. Down-regulation of snaR decreased cell death after 5-FU treatment, which indicates that snaR loss decreases in vitro sensitivity to 5-FU. Our results provide an important insight into the involvement of lncRNAs in 5-FU resistance in colon cancer cells.
Keywords
5-Fluorouracil; cell viability; drug resistance; long non-coding RNAs; snaR;
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1 Shin, YK, Yoo, BC, Hong, YS, Chang, HJ, Jung, KH, Jeong, SY, and Park, JG (2009). Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5-fluorouracil resistance. Electrophoresis. 30, 2182-2192.   DOI   ScienceOn
2 Strathdee, G (2007). Epigenetic markers and response to chemotherapy in cancer. Dis Markers. 23, 43-49.   DOI
3 Mariadason, JM, Arango, D, Shi, Q, Wilson, AJ, Corner, GA, Nicholas, C, Aranes, MJ, Lesser, M, Schwartz, EL, and Augenlicht, LH (2003). Gene expression profiling-based prediction of response of colon carcinoma cells to 5-fluorouracil and camptothecin. Cancer Res. 63, 8791-8812.
4 Mercer, TR, Dinger, ME, and Mattick, JS (2009). Long non-coding RNAs: insights into functions. Nat Rev Genet. 10, 155-159.   DOI   ScienceOn
5 Mishra, PJ (2012). The miRNA-drug resistance connection: a new era of personalized medicine using noncoding RNA begins. Pharmacogenomics. 13, 1321-1324.   DOI   ScienceOn
6 Mishra, PJ, and Bertino, JR (2009). MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics. 10, 399-416.   DOI   ScienceOn
7 Ooyama, A, Takechi, T, Toda, E, Nagase, H, Okayama, Y, Kitazato, K, Sugimoto, Y, Oka, T, and Fukushima, M (2006). Gene expression analysis using human cancer xenografts to identify novel predictive marker genes for the efficacy of 5-fluorouracil-based drugs. Cancer Sci. 97, 510-522.   DOI   ScienceOn
8 Park, JG, Oie, HK, Sugarbaker, PH, Henslee, JG, Chen, TR, Johnson, BE, and Gazdar, A (1987). Characteristics of cell lines established from human colorectal carcinoma. Cancer Res. 47, 6710-6718.
9 Parrott, AM, and Mathews, MB (2007). Novel rapidly evolving hominid RNAs bind nuclear factor 90 and display tissue-restricted distribution. Nucleic Acids Res. 35, 6249-6258.   DOI   ScienceOn
10 Xu, X, Chen, H, Lin, Y, Hu, Z, Mao, Y, Wu, J, Xu, X, Zhu, Y, Li, S, and Zheng, X (2013). MicroRNA-409-3p inhibits migration and invasion of bladder cancer cells via targeting c-Met. Mol Cells. 36, 62-68.   DOI
11 Zhang, N, Yin, Y, Xu, SJ, and Chen, WS (2008). 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules. 13, 1551-1569.   DOI   ScienceOn
12 Zheng, T, Wang, J, Chen, X, and Liu, L (2010). Role of micro-RNA in anticancer drug resistance. Int J Cancer. 126, 2-10.   DOI   ScienceOn
13 Parrott, AM, Tsai, M, Batchu, P, Ryan, K, Ozer, HL, Tian, B, and Mathews, MB (2011). The evolution and expression of the snaR family of small non-coding RNAs. Nucleic Acids Res. 39, 1485-1500.   DOI   ScienceOn
14 Peters, GJ, Backus, HH, Freemantle, S, van Triest, B, Codacci-Pisanelli, G, van der Wilt, CL, Smid, K, Lunec, J, Calvert, AH, and Marsh, S (2002). Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim Biophys Acta. 1587, 194-205.   DOI   ScienceOn
15 Raguz, S, and Yague, E (2008). Resistance to chemotherapy: new treatments and novel insights into an old problem. Br J Cancer. 99, 387-391.   DOI   ScienceOn
16 Ganguly, A, Banerjee, K, Chakraborty, P, Das, S, Sarkar, A, Hazra, A, Banerjee, M, Maity, A, Chatterjee, M, and Mondal, NB (2011). Overcoming multidrug resistance (MDR) in cancer in virto and in vivo by a quinoline derivative. Biomed Pharmacother. 65, 387-394.   DOI   ScienceOn
17 Roberti, A, La Sala, D, and Cinti, C (2006). Multiple genetic and epigenetic interacting mechanisms contribute to clonally selection of drug-resistant tumors: current views and new therapeutic prospective. J Cell Physiol. 207, 571-581.   DOI   ScienceOn
18 Rukov, JL, and Shomron, N (2011). MicroRNA pharmacogenomics: post-transcriptional regulation of drug response. Trends Mol Med. 17, 412-423.   DOI   ScienceOn
19 Shin, YK, Yoo, BC, Chang, HJ, Jeon, E, Hong, SH, Jung, MS, Lim, SJ, and Park, JG (2005). Down-regulation of mitochondrial F1F0-ATP synthase in human colon cancer cells with induced 5-fluorouracil resistance. Cancer Res. 65, 3162-3170.
20 Gibb, EA, Brown, CJ, and Lam, WL (2011). The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 10, 38.   DOI   ScienceOn
21 Glasspool, RM, Teodoridis, JM, and Brown, R (2006). Epigenetics as a mechanism driving polygenic clinical drug resistance. Br J Cancer. 94, 1087-1092.   DOI   ScienceOn
22 Batista, PJ, and Chang, HY (2013). Long noncoding RNAs: cellular address codes in development and disease. Cell. 152, 1298-1307.   DOI   ScienceOn
23 Taft, RJ, Pang, KC, Mercer, TR, Dinger, M, and Mattick, JS (2010). Non-coding RNAs: regulators of disease. J Pathol. 220, 126-139.   DOI   ScienceOn
24 Whitehead, J, Pandey, GK, and Kanduri, C (2009). Regulation of the mammalian epigenome by long noncoding RNAs. Biochim Biophys Acta. 1790, 936-947.   DOI   ScienceOn
25 Tan, DS, Gerlinger, M, Teh, BT, and Swanton, C (2010). Anticancer drug resistance: understanding the mechanisms through the use of integrative genomics and functional RNA interference. Eur J Cancer. 46, 2166-2177.   DOI   ScienceOn
26 Wang, KC, and Chang, HY (2011). Molecular mechanisms of long noncoding RNAs. Mol Cell. 43, 904-914.   DOI   ScienceOn
27 Wang, Z, Li, Y, Ahmad, A, Azmi, AS, Kong, D, Banerjee, S, and Sarkar, FH (2010). Targeting miRNAs involved in cancer stem cell and EMT regulation: an emerging concept in overcoming drug resistance. Drug Resist Updat. 13, 109-118.   DOI   ScienceOn
28 Wilusz, JE, Sunwoo, H, and Spector, DL (2009). Long noncoding RNAs: functional surprises from the RNA world. Genes Dev. 23, 1494-1504.   DOI   ScienceOn
29 Kurokawa, K, Tanahashi, T, Iima, T, Yamamoto, Y, Akaike, Y, Nishida, K, Masuda, K, Kuwano, Y, Murakami, Y, and Fukushima, M (2012). Role of miR-19b and its target mRNAs in 5-fluorouracil resistance in colon cancer cells. J Gastroenterol. 47, 883-895.   DOI   ScienceOn
30 Liu, Z, Sun, M, Lu, K, Liu, J, Zhang, M, Wu, W, De, W, Wang, Z, and Wang, R (2013). The long noncoding RNA HOTAIR contributes to cisplatin resistance of human lung adenocarcinoma cells via downregualtion of p21(WAF1/CIP1) expression. PLoS One. 8, e77293.   DOI
31 Ma, J, Dong, C, and Ji, C (2010). MicroRNA and drug resistance. Cancer Gene Ther. 17, 523-531.   DOI   ScienceOn
32 Fatica, A, and Bozzoni, I (2013). Long non-coding RNAs: new players in cell differentiation and development. Nat Rev Genet. 15, 7-21.   DOI
33 Choi, CH, Lee, TB, Lee, YA, Choi, S, and Kim, KJ (2011). Upregulation of cyclooxygenase-2-derived prostaglandin E(2) in colon cancer cells resistant to 5-fluorouracil. J Korean Surg Soc. 81, 115-121.   DOI   ScienceOn
34 Djebali, S, Davis, CA, Merkel, A, Dobin, A, Lassmann, T, Mortazavi, A, Tanzer, A, Lagarde, J, Lin, W, and Schlesinger, F (2012). Landscape of transcription in human cells. Nature. 489, 101-108.   DOI   ScienceOn
35 Esteller, M (2011). Non-coding RNAs in human disease. Nat Rev Genet. 12, 861-874.   DOI   ScienceOn
36 Fojo, T (2007). Multiple paths to a drug resistance phenotype: mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs. Drug Resist Updat. 10, 59-67.   DOI   ScienceOn
37 Fulda, S, Susin, SA, Kroemer, G, and Debatin, KM (1998). Molecular ordering of apoptosis induced by anticancer drugs in neuroblastoma cells. Cancer Res. 58, 4453-4460.
38 International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators (1995). Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet. 345, 939-944.   DOI   ScienceOn
39 Gottesman, MM (2002). Mechanisms of cancer drug resistance. Ann Rev Med. 53, 615-627.   DOI   ScienceOn
40 Grem, JL (2000). 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs. 18, 299-313.   DOI   ScienceOn
41 Jung, GR, Kim, KJ, Choi, CH, Lee, TB, Han, SI, Han, HK, and Lim, SC (2007). Effect of betulinic acid on anticancer drug-resistant colon cancer cells. Basic Clin Pharmacol Toxicol. 101, 277-285.   DOI   ScienceOn
42 Kang, H, Kim, C, Lee, H, Kim, W, and Lee, EK (2013). Post-transcriptional controls by ribonucleoprotein complexes in the acquisition of drug resistance. Int J Mol Sci. 14, 17204-17220.   DOI   ScienceOn
43 Boyer, J, Allen, WL, McLean, EG, Wilson, PM, McCulla, A, Moore, S, Longley, DB, Caldas, C, and Johnston, PG (2006). Pharmacogenomic identification of novel determinants of response to chemotherapy in colon cancer. Cancer Res. 66, 2765-2777.   DOI   ScienceOn
44 Parrott, AM, and Mathews, MB (2009). snaR genes: recent descendants of Alu involved in the evolution of chorionic gonadotropins. Cold Spring Harbor Symp Quant Biol. 74, 363-373.   DOI
45 Rinn, JL, and Chang, HY (2012). Genome regulation by long noncoding RNAs. Ann Rev Biochem. 81, 145-166.   DOI   ScienceOn
46 Fan, Y, Shen, B, Tan, M, Mu, X, Qin, Y, Zhang, F, and Liu, Y (2014). Long non-coding RNA UCA1 increases chemoresistances of bladder cancer cells by regulating Wnt signaling. FEBS J. 281, 1750-1758.   DOI   ScienceOn
47 Karasawa, H, Miura, K, Fujibuchi, W, Ishida, K, Kaneko, N, Kinouchi, M, Okabe, M, Ando, T, Murata, Y, and Sasaki, H (2009). Down-regulation of cIAP2 enhances 5-FU sensitivity through the apoptotic pathway in human colon cancer cells. Cancer Sci. 100, 903-913.   DOI   ScienceOn
48 Oh, JH, Ku, JL, Yoon, KA, Kwon, HJ, Kim, WH, Park, HS, Yeo, KS, Song, SY, Chung, JK, and Park, JG (1999). Establishment and characterization of 12 human colorectal-carcinoma cell lines. International journal of cancer. J Int Cancer. 81, 902-910.   DOI   ScienceOn