In silico Analysis of Single Nucleotide Polymorphisms Associated with MicroRNA
Regulating 5-fluorouracil Resistance in Colorectal Cancer

Seyed    Hamid    Moosavy; Shabnaz       Koochakkhani; Mahdi       Barazesh; Shiva       Mohammadi; Khadijeh       Ahmadi; Behnaz    Rahnama    Inchehsablagh; Soudabeh       Kavousipour; Ebrahim      Eftekhar; Pooneh       Mokaram
doi:10.2174/1570180818666210930161618
Abstract

Background: Due to the broad influence and reversible nature of microRNA (miRNA) on the expression and regulation of target genes, researchers suggest that miRNAs and single nucleotide polymorphisms (SNPs) in miRNA genes interfere with 5-fluorouracil (5-FU) drug resistance in colorectal cancer chemotherapy.
Methods: Computational assessment and cataloging of miRNA gene polymorphisms that target mRNA transcripts directly or indirectly through regulation of 5-FU chemoresistance in CRC were screened out by applying various universally accessible datasets such as miRNA SNP3.0 software.
Results: 1255 SNPs in 85 miRNAs affecting 5-FU resistance (retrieved from literature) were detected. Computational analysis showed that 167 from 1255 SNPs alter microRNA expression levels leading to inadequate response to 5-FU resistance in CRC. Among these 167 SNPs, 39 were located in the seed region of 25/85 miRNA and were more critical than other SNPs. Has-miR-320a-5p with 4 SNP in seed region was miRNA with the most number of SNPs. On the other hand, it has been identified that proteoglycan in cancer, adherents junction, ECM-receptor interaction, Hippo signaling pathway, TGF-beta signaling cascade, biosynthesis of fatty acid, and fatty acid metabolism were the most important pathways targeted by these 85 predicted miRNAs.
Conclusion: Our data suggest 39 SNPs in the seed region of 25 miRNAs as catalog in miRNA genes that control the 5-FU resistance in CRC. These data also identify the most important pathways regulated by miRNA.
Keywords: 5-fluorouracil, colorectal cancer, single nucleotide polymorphisms, microRNA, chemoresistance, ECM-receptor.
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Graphical Abstract

[1] 
Chen, B.; Xia, Z.; Deng, Y-N.; Yang, Y.; Zhang, P.; Zhu, H.; Xu, N.; Liang, S. Emerging microRNA biomarkers for colorectal cancer diagnosis and prognosis. Open Biol.,  2019, 9(1), 180212.
[http://dx.doi.org/10.1098/rsob.180212] [PMID:  30958116] 
[2] 
Sabeti Aghabozorgi, A.; Moradi Sarabi, M.; Jafarzadeh-Esfehani, R.; Koochakkhani, S.; Hassanzadeh, M.; Kavousipour, S.; Eftekhar, E. Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of micro-ribonucleic acids. World J. Gastrointest. Oncol.,  2020, 12(9), 942-956.
[http://dx.doi.org/10.4251/wjgo.v12.i9.942] [PMID:  33005290] 
[3] 
Moradi Sarabi, M.; Mohammadrezaei Khorramabadi, R.; Zare, Z.; Eftekhar, E. Polyunsaturated fatty acids and DNA methylation in colorectal cancer. World J. Clin. Cases,  2019, 7(24), 4172-4185.
[http://dx.doi.org/10.12998/wjcc.v7.i24.4172] [PMID:  31911898] 
[4] 
Giacchetti, S.; Perpoint, B.; Zidani, R.; Le Bail, N.; Faggiuolo, R.; Focan, C.; Chollet, P.; Llory, J.F.; Letourneau, Y.; Coudert, B.; Bertheaut-Cvitkovic, F.; Larregain-Fournier, D.; Le Rol, A.; Walter, S.; Adam, R.; Misset, J.L.; Lévi, F. Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer. J. Clin. Oncol.,  2000, 18(1), 136-147.
[http://dx.doi.org/10.1200/JCO.2000.18.1.136] [PMID:  10623704] 
[5] 
Douillard, J.Y.; Cunningham, D.; Roth, A.D.; Navarro, M.; James, R.D.; Karasek, P.; Jandik, P.; Iveson, T.; Carmichael, J.; Alakl, M.; Gruia, G.; Awad, L.; Rougier, P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: A multicentre randomised trial. Lancet,  2000, 355(9209), 1041-1047.
[http://dx.doi.org/10.1016/S0140-6736(00)02034-1] [PMID:  10744089] 
[6] 
Tauriello, D.V.; Calon, A.; Lonardo, E.; Batlle, E. Determinants of metastatic competency in colorectal cancer. Mol. Oncol.,  2017, 11(1), 97-119.
[http://dx.doi.org/10.1002/1878-0261.12018] [PMID:  28085225] 
[7] 
Rahman, M.M.; Brane, A.C.; Tollefsbol, T.O. MicroRNAs and epigenetics strategies to reverse breast cancer. Cells,  2019, 8(10), 1214.
[http://dx.doi.org/10.3390/cells8101214] [PMID:  31597272] 
[8] 
Dexheimer, P.J.; Cochella, L. MicroRNAs: From mechanism to organism. Front. Cell Dev. Biol.,  2020, 8, 409.
[http://dx.doi.org/10.3389/fcell.2020.00409] [PMID:  32582699] 
[9] 
Lujambio, A.; Lowe, S.W. The microcosmos of cancer. Nature,  2012, 482(7385), 347-355.
[http://dx.doi.org/10.1038/nature10888] [PMID:  22337054] 
[10] 
Lewis, B.P.; Burge, C.B.; Bartel, D.P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell,  2005, 120(1), 15-20.
[11] 
Ju, J. Implications of miRNAs in colorectal cancer chemoresistance. Int. Drug Discov.,  2011, 2011
[12] 
Jin, Y.; Lee, C.G. Single nucleotide polymorphisms associated with microRNA regulation. Biomolecules,  2013, 3(2), 287-302.
[http://dx.doi.org/10.3390/biom3020287] [PMID:  24970168] 
[13] 
Nguyen, T.T.N.; Tran, M.T.H.; Nguyen, V.T.L.; Nguyen, U.D.P.; Nguyen, G.D.T.; Huynh, L.H.; Nguyen, H.T. Single nucleotide polymorphisms in microRNAs action as biomarkers for breast cancer. Turk. J. Biol.,  2020, 44(5), 284-294.
[http://dx.doi.org/10.3906/biy-2004-78] [PMID:  33110366] 
[14] 
Mates, I.N.; Jinga, V.; Csiki, I.E.; Mates, D.; Dinu, D.; Constantin, A.; Jinga, M. Single nucleotide polymorphisms in colorectal cancer: Associations with tumor site and TNM stage. J. Gastrointestin. Liver Dis.,  2012, 21(1), 45-52.
[PMID:  22457859] 
[15] 
Nahon, P.; Zucman-Rossi, J. Single nucleotide polymorphisms and risk of hepatocellular carcinoma in cirrhosis. J. Hepatol.,  2012, 57(3), 663-674.
[http://dx.doi.org/10.1016/j.jhep.2012.02.035] [PMID:  22609306] 
[16] 
Georges, M.; Coppieters, W.; Charlier, C. Polymorphic miRNA-mediated gene regulation: contribution to phenotypic variation and disease. Curr. Opin. Genet. Dev.,  2007, 17(3), 166-176.
[http://dx.doi.org/10.1016/j.gde.2007.04.005] [PMID:  17467975] 
[17] 
SiamiGorji, S.; Jorjani, I.; Tahamtan, A.; Moradi, A. Effects of microRNAs polymorphism in cancer progression. Med. J. Islam. Repub. Iran,  2020, 34, 3.
[PMID:  32284927] 
[18] 
Kunej, T.; Godnic, I.; Horvat, S.; Zorc, M.; Calin, G.A. Cross talk between microRNA and coding cancer genes. Cancer J.,  2012, 18(3), 223-231.
[http://dx.doi.org/10.1097/PPO.0b013e318258b771] [PMID:  22647358] 
[19] 
Hu, Z.; Bruno, A.E. The Influence of 3¢ UTRs on MicroRNA function inferred from human SNP data. Comp. Funct. Genomics,  2011, 2011, 910769.
[PMID:  22110399] 
[20] 
Moszyńska, A.; Gebert, M.; Collawn, J.F.; Bartoszewski, R. SNPs in microRNA target sites and their potential role in human disease. Open Biol.,  2017, 7(4), 170019.
[http://dx.doi.org/10.1098/rsob.170019] [PMID:  28381629] 
[21] 
Richardson, K.; Lai, C-Q.; Parnell, L.D.; Lee, Y-C.; Ordovas, J.M. A genome-wide survey for SNPs altering microRNA seed sites identifies functional candidates in GWAS. BMC Genomics,  2011, 12(1), 1-14.
[http://dx.doi.org/10.1186/1471-2164-12-504] 
[22] 
Gong, J.; Tong, Y.; Zhang, H.M.; Wang, K.; Hu, T.; Shan, G.; Sun, J.; Guo, A.Y. Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNA target binding and biogenesis. Hum. Mutat.,  2012, 33(1), 254-263.
[http://dx.doi.org/10.1002/humu.21641] [PMID:  22045659] 
[23] 
Vlachos, I.S.; Zagganas, K.; Paraskevopoulou, M.D.; Georgakilas, G.; Karagkouni, D.; Vergoulis, T.; Dalamagas, T.; Hatzigeorgiou, A.G. DIANA-miRPath v3.0: deciphering microRNA function with experimental support. Nucleic Acids Res.,  2015, 43(W1), W460-6.
[http://dx.doi.org/10.1093/nar/gkv403] [PMID:  25977294] 
[24] 
Ryan, B.M.; Robles, A.I.; Harris, C.C. Genetic variation in microRNA networks: the implications for cancer research. Nat. Rev. Cancer,  2010, 10(6), 389-402.
[http://dx.doi.org/10.1038/nrc2867] [PMID:  20495573] 
[25] 
Króliczewski, J.; Sobolewska, A.; Lejnowski, D.; Collawn, J.F.; Bartoszewski, R. microRNA single polynucleotide polymorphism influences on microRNA biogenesis and mRNA target specificity. Gene,  2018, 640, 66-72.
[http://dx.doi.org/10.1016/j.gene.2017.10.021] [PMID:  29032146] 
[26] 
Marjaneh, R.M.; Khazaei, M.; Ferns, G.A.; Avan, A.; Aghaee-Bakhtiari, S.H. The role of microRNAs in 5-FU resistance of colorectal cancer: Possible mechanisms. J. Cell. Physiol.,  2019, 234(3), 2306-2316.
[http://dx.doi.org/10.1002/jcp.27221] [PMID:  30191973] 
[27] 
Jevsinek Skok, D.; Godnic, I.; Zorc, M.; Horvat, S.; Dovc, P.; Kovac, M.; Kunej, T. Genome-wide In silico screening for microRNA genetic variability in livestock species. Anim. Genet.,  2013, 44(6), 669-677.
[http://dx.doi.org/10.1111/age.12072] [PMID:  23865691] 
[28] 
Hill, C.G.; Jabbari, N.; Matyunina, L.V.; McDonald, J.F. Functional and evolutionary significance of human microRNA seed region mutations. PLoS One,  2014, 9(12), e115241.
[http://dx.doi.org/10.1371/journal.pone.0115241] [PMID:  25501359] 
[29] 
Hao, Y.; Baker, D.; Ten Dijke, P. TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. Int. J. Mol. Sci.,  2019, 20(11), 2767.
[http://dx.doi.org/10.3390/ijms20112767] [PMID:  31195692] 
[30] 
Jayachandran, A.; Anaka, M.; Prithviraj, P.; Hudson, C.; McKeown, S.J.; Lo, P.H.; Vella, L.J.; Goding, C.R.; Cebon, J.; Behren, A. Thrombospondin 1 promotes an aggressive phenotype through epithelial-to-mesenchymal transition in human melanoma. Oncotarget,  2014, 5(14), 5782-5797.
[http://dx.doi.org/10.18632/oncotarget.2164] [PMID:  25051363] 
[31] 
Wang, W.; Zhao, L.; Wei, X.; Wang, L.; Liu, S.; Yang, Y.; Wang, F.; Sun, G.; Zhang, J.; Ma, Y.; Zhao, Y.; Yu, J. MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells. Sci. Rep.,  2016, 6(1), 27641.
[http://dx.doi.org/10.1038/srep27641] [PMID:  27279541] 
[32] 
Slabáková, E.; Culig, Z.; Remšík, J.; Souček, K. Alternative mechanisms of miR-34a regulation in cancer. Cell Death Dis.,  2017, 8(10), e3100-e3100.
[http://dx.doi.org/10.1038/cddis.2017.495] [PMID:  29022903] 
[33] 
Kent, O.A.; Fox-Talbot, K.; Halushka, M.K. RREB1 repressed miR-143/145 modulates KRAS signaling through downregulation of multiple targets. Oncogene,  2013, 32(20), 2576-2585.
[http://dx.doi.org/10.1038/onc.2012.266] [PMID:  22751122] 
[34] 
Yan, B.; Guo, Q.; Fu, F.J.; Wang, Z.; Yin, Z.; Wei, Y.B.; Yang, J.R. The role of miR-29b in cancer: regulation, function, and signaling. OncoTargets Ther.,  2015, 8, 539-548.
[PMID:  25767398] 
[35] 
Moradi-Marjaneh, R.; Khazaei, M.; Ferns, G.A.; Aghaee-Bakhtiari, S.H. The role of TGF-β signaling regulatory MicroRNAs in the pathogenesis of colorectal cancer. Curr. Pharm. Des.,  2018, 24(39), 4611-4618.
[http://dx.doi.org/10.2174/1381612825666190110150705] [PMID:  30636580] 
[36] 
Liu, J.; Huang, Y.; Wang, H.; Wu, D. MiR-106a-5p promotes 5-FU resistance and the metastasis of colorectal cancer by targeting TGFβR2. Int. J. Clin. Exp. Pathol.,  2018, 11(12), 5622-5634.
[PMID:  31949649] 
[37] 
Romano, G.; Santi, L.; Bianco, M.R.; Giuffrè, M.R.; Pettinato, M.; Bugarin, C.; Garanzini, C.; Savarese, L.; Leoni, S.; Cerrito, M.G.; Leone, B.E.; Gaipa, G.; Grassilli, E.; Papa, M.; Lavitrano, M.; Giovannoni, R. The TGF-β pathway is activated by 5-fluorouracil treatment in drug resistant colorectal carcinoma cells. Oncotarget,  2016, 7(16), 22077-22091.
[http://dx.doi.org/10.18632/oncotarget.7895] [PMID:  26956045] 
[38] 
Gordian, E.; Welsh, E.A.; Gimbrone, N.; Siegel, E.M.; Shibata, D.; Creelan, B.C.; Cress, W.D.; Eschrich, S.A.; Haura, E.B.; Muñoz-Antonia, T. Transforming growth factor β-induced epithelial-to-mesenchymal signature predicts metastasis-free survival in non-small cell lung cancer. Oncotarget,  2019, 10(8), 810-824.
[http://dx.doi.org/10.18632/oncotarget.26574] [PMID:  30783512] 
[39] 
Toba-Ichihashi, Y.; Yamaoka, T.; Ohmori, T.; Ohba, M. Up-regulation of Syndecan-4 contributes to TGF-β1-induced epithelial to mesenchymal transition in lung adenocarcinoma A549 cells. Biochem. Biophys. Rep.,  2015, 5, 1-7.
[http://dx.doi.org/10.1016/j.bbrep.2015.11.021] [PMID:  28955801] 
[40] 
Yoo, J.; Jeong, M.J.; Cho, H.J.; Oh, E.S.; Han, M.Y. Dynamin II interacts with syndecan-4, a regulator of focal adhesion and stress-fiber formation. Biochem. Biophys. Res. Commun.,  2005, 328(2), 424-431.
[http://dx.doi.org/10.1016/j.bbrc.2004.12.179] [PMID:  15694365] 
[41] 
Gopal, S.; Multhaupt, H.A.B.; Pocock, R.; Couchman, J.R. Cell-extracellular matrix and cell-cell adhesion are linked by syndecan-4. Matrix Biol.,  2017, 60-61, 57-69.
[http://dx.doi.org/10.1016/j.matbio.2016.10.006] [PMID:  27751945] 
[42] 
Yu, F.X.; Zhao, B.; Guan, K.L. Hippo pathway in organ size control, tissue homeostasis, and cancer. Cell,  2015, 163(4), 811-828.
[http://dx.doi.org/10.1016/j.cell.2015.10.044] [PMID:  26544935] 
[43] 
Wan, L.Y.; Deng, J.; Xiang, X.J.; Zhang, L.; Yu, F.; Chen, J.; Sun, Z.; Feng, M.; Xiong, J.P. miR-320 enhances the sensitivity of human colon cancer cells to chemoradiotherapy in vitro by targeting FOXM1. Biochem. Biophys. Res. Commun.,  2015, 457(2), 125-132.
[http://dx.doi.org/10.1016/j.bbrc.2014.11.039] [PMID:  25446103] 
[44] 
Kjersem, J.B.; Ikdahl, T.; Lingjaerde, O.C.; Guren, T.; Tveit, K.M.; Kure, E.H. Plasma microRNAs predicting clinical outcome in metastatic colorectal cancer patients receiving first-line oxaliplatin-based treatment. Mol. Oncol.,  2014, 8(1), 59-67.
[http://dx.doi.org/10.1016/j.molonc.2013.09.001] [PMID:  24119443] 
[45] 
To, K.K.; Tong, C.W.; Wu, M.; Cho, W.C. MicroRNAs in the prognosis and therapy of colorectal cancer: From bench to bedside. World J. Gastroenterol.,  2018, 24(27), 2949-2973.
[http://dx.doi.org/10.3748/wjg.v24.i27.2949] [PMID:  30038463] 
[46] 
Svoboda, M.; Sana, J.; Fabian, P.; Kocakova, I.; Gombosova, J.; Nekvindova, J.; Radova, L.; Vyzula, R.; Slaby, O. MicroRNA expression profile associated with response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients. Radiat. Oncol.,  2012, 7, 195.
[http://dx.doi.org/10.1186/1748-717X-7-195] [PMID:  23167930] 
[47] 
Yu, T.; Guo, F.; Yu, Y.; Sun, T.; Ma, D.; Han, J.; Qian, Y.; Kryczek, I.; Sun, D.; Nagarsheth, N.; Chen, Y.; Chen, H.; Hong, J.; Zou, W.; Fang, J.Y. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell,  2017, 170(3), 548-563.e16.
[http://dx.doi.org/10.1016/j.cell.2017.07.008] [PMID:  28753429] 
[48] 
Zhang, Y.; Talmon, G.; Wang, J. MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer. Cell Death Dis.,  2015, 6(8), e1845.
[http://dx.doi.org/10.1038/cddis.2015.200] [PMID:  26247730] 
[49] 
Zhang, Y.; Geng, L.; Talmon, G.; Wang, J. MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer. J. Biol. Chem.,  2015, 290(10), 6215-6225.
[http://dx.doi.org/10.1074/jbc.M114.620252] [PMID:  25616665] 
[50] 
Nishida, N.; Yamashita, S.; Mimori, K.; Sudo, T.; Tanaka, F.; Shibata, K.; Yamamoto, H.; Ishii, H.; Doki, Y.; Mori, M. MicroRNA-10b is a prognostic indicator in colorectal cancer and confers resistance to the chemotherapeutic agent 5-fluorouracil in colorectal cancer cells. Ann. Surg. Oncol.,  2012, 19(9), 3065-3071.
[http://dx.doi.org/10.1245/s10434-012-2246-1] [PMID:  22322955] 
[51] 
Chai, H.; Liu, M.; Tian, R.; Li, X.; Tang, H. miR-20a targets BNIP2 and contributes chemotherapeutic resistance in colorectal adenocarcinoma SW480 and SW620 cell lines. Acta Biochim. Biophys. Sin. (Shanghai),  2011, 43(3), 217-225.
[http://dx.doi.org/10.1093/abbs/gmq125] [PMID:  21242194] 
[52] 
Boni, V.; Bitarte, N.; Cristobal, I.; Zarate, R.; Rodriguez, J.; Maiello, E.; Garcia-Foncillas, J.; Bandres, E. miR-192/miR-215 influence 5-fluorouracil resistance through cell cycle-mediated mechanisms complementary to its post-transcriptional thymidilate synthase regulation. Mol. Cancer Ther.,  2010, 9(8), 2265-2275.
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0061] [PMID:  20647341] 
[53] 
Yu, W.; Liang, X.; Li, X.; Zhang, Y.; Sun, Z.; Liu, Y.; Wang, J. MicroRNA-195: A review of its role in cancers. OncoTargets Ther.,  2018, 11, 7109-7123.
[http://dx.doi.org/10.2147/OTT.S183600] [PMID:  30410367] 
[54] 
Nijhuis, A.; Thompson, H.; Adam, J.; Parker, A.; Gammon, L.; Lewis, A.; Bundy, J.G.; Soga, T.; Jalaly, A.; Propper, D.; Jeffery, R.; Suraweera, N.; McDonald, S.; Thaha, M.A.; Feakins, R.; Lowe, R.; Bishop, C.L.; Silver, A. Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance. Hum. Mol. Genet.,  2017, 26(8), 1552-1564.
[http://dx.doi.org/10.1093/hmg/ddx059] [PMID:  28207045] 
[55] 
Takahashi, M.; Cuatrecasas, M.; Balaguer, F.; Hur, K.; Toiyama, Y.; Castells, A.; Boland, C.R.; Goel, A. The clinical significance of MiR-148a as a predictive biomarker in patients with advanced colorectal cancer. PLoS One,  2012, 7(10), e46684.
[http://dx.doi.org/10.1371/journal.pone.0046684] [PMID:  23056401] 
[56] 
Song, B.; Wang, Y.; Titmus, M.A.; Botchkina, G.; Formentini, A.; Kornmann, M.; Ju, J. Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol. Cancer,  2010, 9, 96.
[http://dx.doi.org/10.1186/1476-4598-9-96] [PMID:  20433742] 
[57] 
Wang, X.; Jiang, G.; Ren, W.; Wang, B.; Yang, C.; Li, M. LncRNA NEAT1 Regulates 5-Fu sensitivity, apoptosis and invasion in colorectal cancer through the MiR-150-5p/CPSF4 Axis. OncoTargets Ther.,  2020, 13, 6373-6383.
[http://dx.doi.org/10.2147/OTT.S239432] [PMID:  32669857] 
[58] 
Kurokawa, K.; Tanahashi, T.; Iima, T.; Yamamoto, Y.; Akaike, Y.; Nishida, K.; Masuda, K.; Kuwano, Y.; Murakami, Y.; Fukushima, M.; Rokutan, K. Role of miR-19b and its target mRNAs in 5-fluorouracil resistance in colon cancer cells. J. Gastroenterol.,  2012, 47(8), 883-895.
[http://dx.doi.org/10.1007/s00535-012-0547-6] [PMID:  22382630] 
[59] 
Nakagawa, Y.; Kuranaga, Y.; Tahara, T.; Yamashita, H.; Shibata, T.; Nagasaka, M.; Funasaka, K.; Ohmiya, N.; Akao, Y. Induced miR-31 by 5-fluorouracil exposure contributes to the resistance in colorectal tumors. Cancer Sci.,  2019, 110(8), 2540-2548.
[http://dx.doi.org/10.1111/cas.14090] [PMID:  31162779] 
[60] 
Slaby, O.; Calin, G.A. Non-coding RNAs in colorectal cancer; Springer, 2016, Vol. 937, . 
[http://dx.doi.org/10.1007/978-3-319-42059-2_8] 
[61] 
Li, X.; Zhao, H.; Zhou, X.; Song, L. Inhibition of lactate dehydrogenase A by microRNA-34a resensitizes colon cancer cells to 5-fluorouracil. Mol. Med. Rep.,  2015, 11(1), 577-582.
[http://dx.doi.org/10.3892/mmr.2014.2726] [PMID:  25333573] 
[62] 
Liu, R.L.; Dong, Y.; Deng, Y.Z.; Wang, W.J.; Li, W.D. Tumor suppressor miR-145 reverses drug resistance by directly targeting DNA damage-related gene RAD18 in colorectal cancer. Tumour Biol.,  2015, 36(7), 5011-5019.
[http://dx.doi.org/10.1007/s13277-015-3152-5] [PMID:  25913620] 
[63] 
Zhang, J.; Guo, H.; Zhang, H.; Wang, H.; Qian, G.; Fan, X.; Hoffman, A.R.; Hu, J.F.; Ge, S. Putative tumor suppressor miR-145 inhibits colon cancer cell growth by targeting oncogene Friend leukemia virus integration 1 gene. Cancer,  2011, 117(1), 86-95.
[http://dx.doi.org/10.1002/cncr.25522] [PMID:  20737575] 
[64] 
Offer, S.M.; Butterfield, G.L.; Jerde, C.R.; Fossum, C.C.; Wegner, N.J.; Diasio, R.B. microRNAs miR-27a and miR-27b directly regulate liver dihydropyrimidine dehydrogenase expression through two conserved binding sites. Mol. Cancer Ther.,  2014, 13(3), 742-751.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0878] [PMID:  24401318] 
[65] 
Senfter, D.; Holzner, S.; Kalipciyan, M.; Staribacher, A.; Walzl, A.; Huttary, N.; Krieger, S.; Brenner, S.; Jäger, W.; Krupitza, G.; Dolznig, H.; Mader, R.M. Loss of MiR-200 family in 5-fluorouracil resistant colon cancer drives lymphendothelial invasiveness in vitro. Hum. Mol. Genet.,  2015, 24(13), 3689-3698.
[http://dx.doi.org/10.1093/hmg/ddv113] [PMID:  25832648] 
[66] 
Wu, H.; Liang, Y.; Shen, L.; Shen, L. MicroRNA-204 modulates colorectal cancer cell sensitivity in response to 5-fluorouracil-based treatment by targeting high mobility group protein A2. Biol. Open,  2016, 5(5), 563-570.
[http://dx.doi.org/10.1242/bio.015008] [PMID:  27095441] 
[67] 
Wu, H.; Zou, Q.; He, H.; Liang, Y.; Lei, M.; Zhou, Q.; Fan, D.; Shen, L. Long non-coding RNA PCAT6 targets miR-204 to modulate the chemoresistance of colorectal cancer cells to 5-fluorouracil-based treatment through HMGA2 signaling. Cancer Med.,  2019, 8(5), 2484-2495.
[http://dx.doi.org/10.1002/cam4.1809] [PMID:  30938104] 
[68] 
Kim, S-A.; Kim, I.; Yoon, S.K.; Lee, E.K.; Kuh, H-J. Indirect modulation of sensitivity to 5-fluorouracil by microRNA-96 in human colorectal cancer cells. Arch. Pharm. Res.,  2015, 38(2), 239-248.
[http://dx.doi.org/10.1007/s12272-014-0528-9] [PMID:  25502560] 
[69] 
Chai, J.; Dong, W.; Xie, C.; Wang, L.; Han, D.L.; Wang, S.; Guo, H.L.; Zhang, Z.L. MicroRNA-494 sensitizes colon cancer cells to fluorouracil through regulation of DPYD. IUBMB Life,  2015, 67(3), 191-201.
[http://dx.doi.org/10.1002/iub.1361] [PMID:  25873402] 
[70] 
Miyazaki, S.; Yamamoto, H.; Miyoshi, N.; Wu, X.; Ogawa, H.; Uemura, M.; Nishimura, J.; Hata, T.; Takemasa, I.; Mizushima, T.; Konno, M.; Doki, Y.; Mori, M.; Ishii, H. A cancer reprogramming method using MicroRNAs as a novel therapeutic approach against colon cancer. Ann. Surg. Oncol.,  2015, 22(3), S1394-S1401.
[http://dx.doi.org/10.1245/s10434-014-4217-1] [PMID: 25384704] 
[71] 
To, K.K.; Leung, W.W.; Ng, S.S. Exploiting a novel miR-519c-HuR-ABCG2 regulatory pathway to overcome chemoresistance in colorectal cancer. Exp. Cell Res.,  2015, 338(2), 222-231.
[http://dx.doi.org/10.1016/j.yexcr.2015.09.011] [PMID:  26386386] 
[72] 
Amankwatia, E.B.; Chakravarty, P.; Carey, F.A.; Weidlich, S.; Steele, R.J.; Munro, A.J.; Wolf, C.R.; Smith, G. MicroRNA-224 is associated with colorectal cancer progression and response to 5-fluorouracil-based chemotherapy by KRAS-dependent and -independent mechanisms. Br. J. Cancer,  2015, 112(9), 1480-1490.
[http://dx.doi.org/10.1038/bjc.2015.125] [PMID:  25919696] 
[73] 
Wang, T.; Ma, L.; Li, W.; Ding, L.; Gao, H. MicroRNA-498 reduces the proliferation and invasion of colorectal cancer cells via targeting Bcl-2. FEBS Open Bio,  2020, 10(1), 168-175.
[http://dx.doi.org/10.1002/2211-5463.12767] [PMID:  31769193] 
[74] 
Liu, L.; Zheng, W.; Song, Y.; Du, X.; Tang, Y.; Nie, J.; Han, W. miRNA-497 enhances the sensitivity of colorectal cancer cells to neoadjuvant chemotherapeutic drug. Curr. Protein Pept. Sci.,  2015, 16(4), 310-315.
[http://dx.doi.org/10.2174/138920371604150429154142] [PMID:  25929865] 
[75] 
Zhang, Y.; Hu, X.; Miao, X.; Zhu, K.; Cui, S.; Meng, Q.; Sun, J.; Wang, T. MicroRNA-425-5p regulates chemoresistance in colorectal cancer cells via regulation of Programmed Cell Death 10. J. Cell. Mol. Med.,  2016, 20(2), 360-369.
[http://dx.doi.org/10.1111/jcmm.12742] [PMID:  26647742] 
[76] 
Zhang, H.; Tang, J.; Li, C.; Kong, J.; Wang, J.; Wu, Y.; Xu, E.; Lai, M. MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells. Cancer Lett.,  2015, 356(2 Pt B), 781-790.
[http://dx.doi.org/10.1016/j.canlet.2014.10.029] [PMID:  25449431] 
[77] 
Jin, Y.; Jiang, Z.; Guan, X.; Chen, Y.; Tang, Q.; Wang, G.; Wang, X. miR-450b-5p suppresses stemness and the development of chemoresistance by targeting SOX2 in colorectal cancer. DNA Cell Biol.,  2016, 35(5), 249-256.
[http://dx.doi.org/10.1089/dna.2015.3120] [PMID:  26845645] 
[78] 
Cao, S.; Lin, L.; Xia, X.; Wu, H. MicroRNA-761 promotes the sensitivity of colorectal cancer cells to 5-Fluorouracil through targeting FOXM1. Oncotarget,  2017, 9(1), 321-331.
[http://dx.doi.org/10.18632/oncotarget.20109] [PMID:  29416616] 
[79] 
Li, Q.; Liang, X.; Wang, Y.; Meng, X.; Xu, Y.; Cai, S.; Wang, Z.; Liu, J.; Cai, G. miR-139-5p inhibits the epithelial-mesenchymal transition and enhances the chemotherapeutic sensitivity of colorectal cancer cells by downregulating BCL2. Sci. Rep.,  2016, 6(1), 27157.
[http://dx.doi.org/10.1038/srep27157] [PMID:  27244080] 
[80] 
Rossi, L.; Bonmassar, E.; Faraoni, I. Modification of miR gene expression pattern in human colon cancer cells following exposure to 5-fluorouracil in vitro. Pharmacol. Res.,  2007, 56(3), 248-253.
[http://dx.doi.org/10.1016/j.phrs.2007.07.001] [PMID:  17702597] 
[81] 
Simmer, F.; Venderbosch, S.; Dijkstra, J.R.; Vink-Börger, E.M.; Faber, C.; Mekenkamp, L.J.; Koopman, M.; De Haan, A.F.; Punt, C.J.; Nagtegaal, I.D. MicroRNA-143 is a putative predictive factor for the response to fluoropyrimidine-based chemotherapy in patients with metastatic colorectal cancer. Oncotarget,  2015, 6(26), 22996-23007.
[http://dx.doi.org/10.18632/oncotarget.4035] [PMID:  26392389] 
[82] 
Li, X.; Li, X.; Liao, D.; Wang, X.; Wu, Z.; Nie, J.; Bai, M.; Fu, X.; Mei, Q.; Han, W. Elevated microRNA-23a expression enhances the chemoresistance of colorectal cancer cells with microsatellite instability to 5-fluorouracil by directly targeting ABCF1. Curr. Protein Pept. Sci.,  2015, 16(4), 301-309.
[http://dx.doi.org/10.2174/138920371604150429153309] [PMID:  25929864] 
[83] 
Song, B.; Wang, Y.; Xi, Y.; Kudo, K.; Bruheim, S.; Botchkina, G.I.; Gavin, E.; Wan, Y.; Formentini, A.; Kornmann, M.; Fodstad, O.; Ju, J. Mechanism of chemoresistance mediated by miR-140 in human osteosarcoma and colon cancer cells. Oncogene,  2009, 28(46), 4065-4074.
[http://dx.doi.org/10.1038/onc.2009.274] [PMID:  19734943] 
[84] 
Sun, Q.; Gu, H.; Zeng, Y.; Xia, Y.; Wang, Y.; Jing, Y.; Yang, L.; Wang, B. Hsa-mir-27a genetic variant contributes to gastric cancer susceptibility through affecting miR-27a and target gene expression. Cancer Sci.,  2010, 101(10), 2241-2247.
[http://dx.doi.org/10.1111/j.1349-7006.2010.01667.x] [PMID:  20666778] 
[85] 
Wang, J.Y.; Zhang, Q.; Wang, D.D.; Yan, W.; Sha, H.H.; Zhao, J.H.; Yang, S.J.; Zhang, H.D.; Hou, J.C.; Xu, H.Z.; He, Y.J.; Hu, J.H.; Zhong, S.L.; Tang, J.H. MiR-29a: A potential therapeutic target and promising biomarker in tumors. Biosci. Rep.,  2018, 38(1), BSR20171265.
[http://dx.doi.org/10.1042/BSR20171265] [PMID:  29217524] 
[86] 
Feng, Y-H.; Wu, C-L.; Shiau, A-L.; Lee, J-C.; Chang, J-G.; Lu, PJ.; Tung, C-L.; Feng, L-Y.; Huang, W-T.; Tsao, C-J. MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells. Int. J. Mol. Med.,  2012, 29(5), 920-926.
[PMID: 22322462] 
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DOI https://dx.doi.org/10.2174/1570180818666210930161618	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X
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In silico Analysis of Single Nucleotide Polymorphisms Associated with MicroRNA Regulating 5-fluorouracil Resistance in Colorectal Cancer

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