HuR as Therapeutic Target in Cancer: What the Future Holds

Dimitrios      Goutas; Alexandros      Pergaris; Constantinos      Giaginis; Stamatios      Theocharis
Abstract

ELAV-like protein 1 or HuR (human antigen R) is an RNA-binding protein that in humans is encoded by the ELAVL1 gene, and one of its best functions is to stabilize mRNAs in order to regulate gene expression. HuR protein overexpression has undoubtedly been linked to an increased risk of tumor growth, progression and metastasis, rendering it a potential therapeutic target candidate in cancer. Novel agents, interfering with HuR expression, have been tested, both in vitro and in vivo, with promising results. The aim of this paper is to review the existing literature regarding the potential agents that could actively act on and inhibit HuR expression. HuR molecule controls the expression of various proto-oncogenes, cytokines and growth factors, representing a major player in tumor progression, invasion and metastasis and constituting an emerging target for cancer therapy. PubMed database was thoroughly searched, and all published articles providing scientific data on molecules that can exhibit antitumorigenic effects via HuR inhibition were included. According to these data, HuR inhibition should be a promising target in cancer therapeutics.
Keywords: HuR protein, cancer therapy, HuR inhibition, small molecules, miRNAs, siRNAs.
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[1] 
Lunde, B.M.; Moore, C.; Varani, G. RNA-binding proteins: Modular design for efficient function. Nat. Rev. Mol. Cell Biol.,  2007, 8(6), 479-490.
[http://dx.doi.org/10.1038/nrm2178] [PMID: 17473849] 
[2] 
Hogan, D.J.; Riordan, D.P.; Gerber, A.P.; Herschlag, D.; Brown, P.O. Diverse RNA-binding proteins interact with functionally related sets of RNAs, suggesting an extensive regulatory system. PLoS Biol.,  2008, 6(10)e255
[http://dx.doi.org/10.1371/journal.pbio.0060255] [PMID: 18959479] 
[3] 
Ma, W.J.; Chung, S.; Furneaux, H. The Elav-like proteins bind to AU-rich elements and to the poly(A) tail of mRNA. Nucleic Acids Res.,  1997, 25(18), 3564-3569.
[http://dx.doi.org/10.1093/nar/25.18.3564] [PMID: 9278474] 
[4] 
Srikantan, S.; Gorospe, M. HuR function in disease. Front. Biosci.(Landmark Ed),  2012, 17, 189-205.
[http://dx.doi.org/10.2741/3921] [PMID: 22201738] 
[5] 
Kotta-Loizou, I.; Giaginis, C.; Theocharis, S. Clinical significance of hur expression in human malignancy. Med. Oncol.,  2014, 31(9), 161.
[http://dx.doi.org/10.1007/s12032-014-0161-y] 
[6] 
Giaginis, C.; Alexandrou, P.; Delladetsima, I.; Karavokyros, I.; Danas, E.; Giagini, A.; Patsouris, E.; Theocharis, S. Clinical significance of hu-antigen receptor (hur) and cyclooxygenase-2 (cox-2) expression in human malignant and benign thyroid lesions. Pathol. Oncol. Res.,  2016, 22(1), 189-196.
[http://dx.doi.org/10.1007/s12253-015-9997-5] [PMID: 26498465] 
[7] 
Giaginis, C.; Sampani, A.; Kotta-Loizou, I.; Giannopoulou, I.; Danas, E.; Politi, E.; Tsourouflis, G.; Kouraklis, G.; Patsouris, E.; Keramopoulos, A.; Nakopoulou, L.; Theocharis, S. Elevated hu-antigen receptor (hur) expression is associated with tumor aggressiveness and poor prognosis but not with cox-2 expression in invasive breast carcinoma patients. Pathol. Oncol. Res.,  2018, 24(3), 631-640.
[http://dx.doi.org/10.1007/s12253-017-0288-1] [PMID: 28808873] 
[8] 
Giaginis, C.; Alexandrou, P.; Tsoukalas, N.; Sfiniadakis, I.; Kavantzas, N.; Agapitos, E.; Patsouris, E.; Theocharis, S. Hu-antigen receptor (HuR) and cyclooxygenase-2 (COX-2) expression in human non-small-cell lung carcinoma: Associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival. Tumour Biol.,  2015, 36(1), 315-327.
[http://dx.doi.org/10.1007/s13277-014-2637-y] [PMID: 25252849] 
[9] 
Yiakouvaki, A.; Dimitriou, M.; Karakasiliotis, I.; Eftychi, C.; Theocharis, S.; Kontoyiannis, D.L. Myeloid cell expression of the RNA-binding protein HuR protects mice from pathologic inflammation and colorectal carcinogenesis. J. Clin. Invest.,  2012, 122(1), 48-61.
[http://dx.doi.org/10.1172/JCI45021] [PMID: 22201685] 
[10] 
Brauß, T.F.; Winslow, S.; Lampe, S.; Scholz, A.; Weigert, A.; Dehne, N.; von Stedingk, K.; Schmid, T.; Brüne, B. The RNA-binding protein HuR inhibits expression of CCL5 and limits recruitment of macrophages into tumors. Mol. Carcinog.,  2017, 56(12), 2620-2629.
[http://dx.doi.org/10.1002/mc.22706] [PMID: 28731284] 
[11] 
Peng, W.; Furuuchi, N.; Aslanukova, L.; Huang, Y-H.; Brown, S.Z.; Jiang, W.; Addya, S.; Vishwakarma, V.; Peters, E.; Brody, J.R.; Dixon, D.A.; Sawicki, J.A. Elevated hur in pancreas promotes a pancreatitis-like inflammatory microenvironment that facilitates tumor development. Mol. Cell. Biol.,  2018, 38(3), e00427-e17.
[http://dx.doi.org/10.1128/MCB.00427-17] [PMID: 29133460] 
[12] 
Goldberg-Cohen, I.; Furneauxb, H.; Levy, A.P.A. A 40-bp RNA element that mediates stabilization of vascular endothelial growth factor mRNA by HuR. J. Biol. Chem.,  2002, 277(16), 13635-13640.
[http://dx.doi.org/10.1074/jbc.M108703200] [PMID: 11834731] 
[13] 
Holmes, B.; Benavides-Serrato, A.; Freeman, R.S.; Landon, K.A.; Bashir, T.; Nishimura, R.N.; Gera, J. mTORC2/AKT/HSF1/HuR constitute a feed-forward loop regulating Rictor expression and tumor growth in glioblastoma. Oncogene,  2018, 37(6), 732-743.
[http://dx.doi.org/10.1038/onc.2017.360] [PMID: 29059166] 
[14] 
Kurosu, T.; Ohga, N.; Hida, Y.; Maishi, N.; Akiyama, K.; Kakuguchi, W.; Kuroshima, T.; Kondo, M.; Akino, T.; Totsuka, Y.; Shindoh, M.; Higashino, F.; Hida, K. HuR keeps an angiogenic switch on by stabilising mRNA of VEGF and COX-2 in tumour endothelium. Br. J. Cancer,  2011, 104(5), 819-829.
[http://dx.doi.org/10.1038/bjc.2011.20] [PMID: 21285980] 
[15] 
Kotta-Loizou, I.; Vasilopoulos, S.N.; Coutts, R.H.A.; Theocharis, S. Current evidence and future perspectives on hur and breast cancer development, prognosis, and treatment.Neoplasia; Neoplasia Press, Inc.: United States, 2016, pp. 674-688.
[16] 
Levidou, G.; Kotta-Loizou, I.; Tasoulas, J.; Papadopoulos, T.; Theocharis, S. Clinical significance and biological role of hur in head and neck carcinomas. Dis. Markers,  2018, 20184020937
[http://dx.doi.org/10.1155/2018/4020937] [PMID: 29619127] 
[17] 
Guo, X.; Wu, Y.; Hartley, R.S. MicroRNA-125a represses cell growth by targeting HuR in breast cancer. RNA Biol.,  2009, 6(5), 575-583.
[http://dx.doi.org/10.4161/rna.6.5.10079] [PMID: 19875930] 
[18] 
Roff, A.N.; Craig, T.J.; August, A.; Stellato, C.; Ishmael, F.T. MicroRNA-570-3p regulates HuR and cytokine expression in airway epithelial cells. Am. J. Clin. Exp. Immunol.,  2014, 3(2), 68-83.
[PMID: 25143867] 
[19] 
Guo, J.; Li, M.; Meng, X.; Sui, J.; Dou, L.; Tang, W.; Huang, X.; Man, Y.; Wang, S.; Li, J. MiR-291b-3p induces apoptosis in liver cell line NCTC1469 by reducing the level of RNA-binding protein HuR. Cell. Physiol. Biochem.,  2014, 33(3), 810-822.
[http://dx.doi.org/10.1159/000358654] [PMID: 24685524] 
[20] 
Guo, X.; Connick, M.C.; Vanderhoof, J.; Ishak, M.A.; Hartley, R.S. MicroRNA-16 modulates HuR regulation of cyclin E1 in breast cancer cells. Int. J. Mol. Sci.,  2015, 16(4), 7112-7132.
[http://dx.doi.org/10.3390/ijms16047112] [PMID: 25830480] 
[21] 
Abdelmohsen, K.; Kim, M.M.; Srikantan, S.; Mercken, E.M.; Brennan, S.E.; Wilson, G.M.; Cabo, Rd.; Gorospe, M. miR-519 suppresses tumor growth by reducing HuR levels. Cell Cycle,  2010, 9(7), 1354-1359.
[http://dx.doi.org/10.4161/cc.9.7.11164] [PMID: 20305372] 
[22] 
Fan, X.C.; Steitz, J.A. HNS, a nuclear-cytoplasmic shuttling sequence in HuR. Proc. Natl. Acad. Sci. USA,  1998, 95(26), 15293-15298.
[http://dx.doi.org/10.1073/pnas.95.26.15293] [PMID: 9860962] 
[23] 
Gallouzi, I.E.; Brennan, C.M.; Steitz, J.A. Protein ligands mediate the CRM1-dependent export of HuR in response to heat shock. RNA,  2001, 7(9), 1348-1361.
[http://dx.doi.org/10.1017/S1355838201016089] [PMID: 11565755] 
[24] 
Rebane, A.; Aab, A.; Steitz, J.A. Transportins 1 and 2 are redundant nuclear import factors for hnRNP A1 and HuR. RNA,  2004, 10(4), 590-599.
[http://dx.doi.org/10.1261/rna.5224304] [PMID: 15037768] 
[25] 
Grammatikakis, I.; Abdelmohsen, K.; Gorospe, M. Posttranslational control of hur function.Wiley Interdisciplinary Reviews: RNA; Blackwell Publishing Ltd, 2017. 
[26] 
Zhu, Z.; Zhao, Y.; Li, J.; Tao, L.; Shi, P.; Wei, Z.; Sheng, X.; Shen, D.; Liu, Z.; Zhou, L.; Tian, C.; Fan, F.; Shen, C.; Zhu, P.; Wang, A.; Chen, W.; Zhao, Q.; Lu, Y. Cryptotanshinone, a novel tumor angiogenesis inhibitor, destabilizes tumor necrosis factor-α mRNA via decreasing nuclear-cytoplasmic translocation of RNA-binding protein HuR. Mol. Carcinog.,  2016, 55(10), 1399-1410.
[http://dx.doi.org/10.1002/mc.22383] [PMID: 26310813] 
[27] 
Blanco, F.F.; Preet, R.; Aguado, A.; Vishwakarma, V.; Stevens, L.E.; Vyas, A.; Padhye, S.; Xu, L.; Weir, S.J.; Anant, S.; Meisner-Kober, N.; Brody, J.R.; Dixon, D.A. Impact of HuR inhibition by the small molecule MS-444 on colorectal cancer cell tumorigenesis. Oncotarget,  2016, 7(45), 74043-74058.
[http://dx.doi.org/10.18632/oncotarget.12189] [PMID: 27677075] 
[28] 
Guo, J.; Lv, J.; Chang, S.; Chen, Z.; Lu, W.; Xu, C.; Liu, M.; Pang, X. Inhibiting cytoplasmic accumulation of HuR synergizes genotoxic agents in urothelial carcinoma of the bladder. Oncotarget,  2016, 7(29), 45249-45262.
[http://dx.doi.org/10.18632/oncotarget.9932] [PMID: 27303922] 
[29] 
Abdelmohsen, K.; Kuwano, Y.; Kim, H.H.; Gorospe, M. Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: Implications for cellular senescence. Biol. Chem.,  2008, 389(3), 243-255.
[http://dx.doi.org/10.1515/BC.2008.022] [PMID: 18177264] 
[30] 
Bartel, D.P. MicroRNAs: Target recognition and regulatory functions. Cell,  2009, 136(2), 215-233.
[http://dx.doi.org/10.1016/j.cell.2009.01.002] [PMID: 19167326] 
[31] 
Meisner, N.C.; Filipowicz, W. Properties of the regulatory RNA-binding protein HuR and its role in controlling miRNA repression. Adv. Exp. Med. Biol.,  2010, 700, 106-123.
[http://dx.doi.org/10.1007/978-1-4419-7823-3_10] [PMID: 21627034] 
[32] 
Muralidharan, R.; Babu, A.; Amreddy, N.; Srivastava, A.; Chen, A.; Zhao, Y.D.; Kompella, U.B.; Munshi, A.; Ramesh, R. Tumor-targeted nanoparticle delivery of hur sirna inhibits lung tumor growth in vitro and in vivo by disrupting the oncogenic activity of the rna-binding protein huR. Mol. Cancer Ther.,  2017, 16(8), 1470-1486.
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0134] [PMID: 28572169] 
[33] 
Wu, X.; Gardashova, G.; Lan, L.; Han, S.; Zhong, C.; Marquez, R.T.; Wei, L.; Wood, S.; Roy, S.; Gowthaman, R.; Karanicolas, J.; Gao, F.P.; Dixon, D.A.; Welch, D.R.; Li, L.; Ji, M.; Aubé, J.; Xu, L. Targeting the interaction between RNA-binding protein HuR and FOXQ1 suppresses breast cancer invasion and metastasis. Commun. Biol.,  2020, 3(1), 193.
[http://dx.doi.org/10.1038/s42003-020-0933-1] [PMID: 32332873] 
[34] 
D’Agostino, V.G.; Lal, P.; Mantelli, B.; Tiedje, C.; Zucal, C.; Thongon, N.; Gaestel, M.; Latorre, E.; Marinelli, L.; Seneci, P.; Amadio, M.; Provenzani, A. Dihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function. Sci. Rep.,  2015, 5, 16478.
[http://dx.doi.org/10.1038/srep16478] [PMID: 26553968] 
[35] 
Lee, C.Y.; Sher, H.F.; Chen, H.W.; Liu, C.C.; Chen, C.H.; Lin, C.S.; Yang, P.C.; Tsay, H.S.; Chen, J.J.W. Anticancer effects of tanshinone I in human non-small cell lung cancer. Mol. Cancer Ther.,  2008, 7(11), 3527-3538.
[http://dx.doi.org/10.1158/1535-7163.MCT-07-2288] [PMID: 19001436] 
[36] 
Kaur, K.; Wu, X.; Fields, J.K.; Johnson, D.K.; Lan, L.; Pratt, M.; Somoza, A.D.; Wang, C.C.C.; Karanicolas, J.; Oakley, B.R.; Xu, L.; De Guzman, R.N. The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA interaction in vitro. PLoS One,  2017, 12(4)e0175471
[http://dx.doi.org/10.1371/journal.pone.0175471] [PMID: 28414767] 
[37] 
Amreddy, N.; Babu, A.; Panneerselvam, J.; Srivastava, A.; Muralidharan, R.; Chen, A.; Zhao, Y.D.; Munshi, A.; Ramesh, R. Chemo-biologic combinatorial drug delivery using folate receptor-targeted dendrimer nanoparticles for lung cancer treatment. Nanomedicine (Lond.),  2018, 14(2), 373-384.
[http://dx.doi.org/10.1016/j.nano.2017.11.010] [PMID: 29155362] 
[38] 
Costantino, C.L.; Witkiewicz, A.K.; Kuwano, Y.; Cozzitorto, J.A.; Kennedy, E.P.; Dasgupta, A.; Keen, J.C.; Yeo, C.J.; Gorospe, M.; Brody, J.R. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR Up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase. Cancer Res.,  2009, 69(11), 4567-4572.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-0371] [PMID: 19487279] 
[39] 
Masaoutis, C.; Korkolopoulou, P.; Theocharis, S. Exosomes in sarcomas: Tiny messengers with broad implications in diagnosis, surveillance, prognosis and treatment. Cancer Lett.,  2019, 449, 172-177.
[40] 
Wang, W.; Yang, X.; Kawai, T.; López de Silanes, I.; Mazan-Mamczarz, K.; Chen, P.; Chook, Y.M.; Quensel, C.; Köhler, M.; Gorospe, M. AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha1: Involvement in the nuclear import of RNA-binding protein HuR. J. Biol. Chem.,  2004, 279(46), 48376-48388.
[http://dx.doi.org/10.1074/jbc.M409014200] [PMID: 15342649] 
[41] 
Martínez-Chantar, M.L.; Vázquez-Chantada, M.; Garnacho, M.; Latasa, M.U.; Varela-Rey, M.; Dotor, J.; Santamaria, M.; Martínez-Cruz, L.A.; Parada, L.A.; Lu, S.C.; Mato, J.M. S-adenosylmethionine regulates cytoplasmic HuR via AMP-activated kinase. Gastroenterology,  2006, 131(1), 223-232.
[http://dx.doi.org/10.1053/j.gastro.2006.04.019] [PMID: 16831604] 
[42] 
Chiou, J.T.; Lee, Y.C.; Huang, C.H.; Shi, Y.J.; Wang, L.J.; Chang, L.S. Autophagic HuR mRNA degradation induces survivin and MCL1 downregulation in YM155-treated human leukemia cells. Toxicol. Appl. Pharmacol.,  2020, 387114857
[http://dx.doi.org/10.1016/j.taap.2019.114857] [PMID: 31837377] 
[43] 
Cheng, Y.C.; Liou, J.P.; Kuo, C.C.; Lai, W.Y.; Shih, K.H.; Chang, C.Y.; Pan, W.Y.; Tseng, J.T.; Chang, J.Y. MPT0B098, a novel microtubule inhibitor that destabilizes the hypoxia-inducible factor-1α mRNA through decreasing nuclear-cytoplasmic translocation of RNA-binding protein HuR. Mol. Cancer Ther.,  2013, 12(7), 1202-1212.
[http://dx.doi.org/10.1158/1535-7163.MCT-12-0778] [PMID: 23619299] 
[44] 
Meisner, N.C.; Hintersteiner, M.; Mueller, K.; Bauer, R.; Seifert, J.M.; Naegeli, H.U.; Ottl, J.; Oberer, L.; Guenat, C.; Moss, S.; Harrer, N.; Woisetschlaeger, M.; Buehler, C.; Uhl, V.; Auer, M. Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR. Nat. Chem. Biol.,  2007, 3(8), 508-515.
[http://dx.doi.org/10.1038/nchembio.2007.14] [PMID: 17632515] 
[45] 
Hostetter, C.; Licata, L.A.; Witkiewicz, A.; Costantino, C.L.; Yeo, C.J.; Brody, J.R.; Keen, J.C. Cytoplasmic accumulation
of the RNA binding protein HuR is central to tamoxifen
resistance in estrogen receptor positive breast cancer
cells. Cancer Biol. Ther.,,  2008, 7(9), 1496-1506.
[http://dx.doi.org/10.4161/cbt.7.9.6490] [PMID: 18769129] 
[46] 
Pryzbylkowski, P.; Obajimi, O.; Keen, J.C. Trichostatin A and 5 Aza-2′ deoxycytidine decrease estrogen receptor mRNA stability in ER positive MCF7 cells through modulation of HuR. Breast Cancer Res. Treat.,  2008, 111(1), 15-25.
[http://dx.doi.org/10.1007/s10549-007-9751-0] [PMID: 17891453] 
[47] 
Lee, J.Y.; Chung, T.W.; Choi, H.J.; Lee, C.H.; Eun, J.S.; Han, Y.T.; Choi, J.Y.; Kim, S.Y.; Han, C.W.; Jeong, H.S.; Ha, K.T. A novel cantharidin analog N-benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR. Biochem. Biophys. Res. Commun.,  2014, 447(2), 371-377.
[http://dx.doi.org/10.1016/j.bbrc.2014.04.035] [PMID: 24735540] 
[48] 
Sun, L.; Zhang, S.; Jiang, Z.; Huang, X.; Wang, T.; Huang, X.; Li, H.; Zhang, L. Triptolide inhibits COX-2 expression by regulating mRNA stability in TNF-α-treated A549 cells. Biochem. Biophys. Res. Commun.,  2011, 416(1-2), 99-105.
[http://dx.doi.org/10.1016/j.bbrc.2011.11.004] [PMID: 22093832] 
[49] 
Mutka, S.C.; Yang, W.Q.; Dong, S.D.; Ward, S.L.; Craig, D.A.; Timmermans, P.B.M.W.M.; Murli, S. Identification of nuclear export inhibitors with potent anticancer activity in vivo. Cancer Res.,  2009, 69(2), 510-517.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0858] [PMID: 19147564] 
[50] 
Doller, A.; Badawi, A.; Schmid, T.; Brauss, T.; Pleli, T.; zu Heringdorf, D.M.; Piiper, A.; Pfeilschifter, J.; Eberhardt, W. The cytoskeletal inhibitors latrunculin A and blebbistatin exert antitumorigenic properties in human hepatocellular carcinoma cells by interfering with intracellular HuR trafficking. Exp. Cell Res.,  2015, 330(1), 66-80.
[http://dx.doi.org/10.1016/j.yexcr.2014.09.010] [PMID: 25240929] 
[51] 
Gabai, V.L.; Meng, L.; Kim, G.; Mills, T.A.; Benjamin, I.J.; Sherman, M.Y. Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR. Mol. Cell. Biol.,  2012, 32(5), 929-940.
[http://dx.doi.org/10.1128/MCB.05921-11] [PMID: 22215620] 
[52] 
Xu, F.; Zhang, X.; Lei, Y.; Liu, X.; Liu, Z.; Tong, T.; Wang, W. Loss of repression of HuR translation by miR-16 may be responsible for the elevation of HuR in human breast carcinoma. J. Cell. Biochem.,  2010, 111(3), 727-734.
[http://dx.doi.org/10.1002/jcb.22762] [PMID: 20626035] 
[53] 
Lal, P.; Cerofolini, L.; D’Agostino, V.G.; Zucal, C.; Fuccio, C.; Bonomo, I.; Dassi, E.; Giuntini, S.; Di Maio, D.; Vishwakarma, V.; Preet, R.; Williams, S.N.; Fairlamb, M.S.; Munk, R.; Lehrmann, E.; Abdelmohsen, K.; Elezgarai, S.R.; Luchinat, C.; Novellino, E.; Quattrone, A.; Biasini, E.; Manzoni, L.; Gorospe, M.; Dixon, D.A.; Seneci, P.; Marinelli, L.; Fragai, M.; Provenzani, A. Regulation of HuR structure and function by dihydrotanshinone-I. Nucleic Acids Res.,  2017, 45(16), 9514-9527.
[http://dx.doi.org/10.1093/nar/gkx623] [PMID: 28934484] 
[54] 
Muralidharan, R.; Mehta, M.; Ahmed, R.; Roy, S.; Xu, L.; Aubé, J.; Chen, A.; Zhao, Y.D.; Herman, T.; Ramesh, R.; Munshi, A. HuR-targeted small molecule inhibitor exhibits cytotoxicity towards human lung cancer cells. Sci. Rep.,  2017, 7(1), 9694.
[http://dx.doi.org/10.1038/s41598-017-07787-4] [PMID: 28855578] 
[55] 
Kaur, K.; Wu, X.; Fields, J.K.; Johnson, D.K.; Lan, L.; Pratt, M.; Somoza, A.D.; Wang, C.C.C.; Karanicolas, J.; Oakley, B.R.; Xu, L.; De Guzman, R.N. The fungal natural product azaphilone-9 binds to HuR and inhibits HuR-RNA interaction in vitro. PLoS One,  2017, 12(4)
[http://dx.doi.org/10.1371/journal.pone.0175471] 
[56] 
D’Agostino, V.G.; Adami, V.; Provenzani, A. A novel high throughput biochemical assay to evaluate the HuR protein-RNA complex formation. PLoS One,  2013, 8(8)e72426
[http://dx.doi.org/10.1371/journal.pone.0072426] [PMID: 23951323] 
[57] 
Kakuguchi, W.; Nomura, T.; Kitamura, T.; Otsuguro, S.; Matsushita, K.; Sakaitani, M.; Maenaka, K.; Tei, K. Suramin, screened from an approved drug library, inhibits HuR functions and attenuates malignant phenotype of oral cancer cells. Cancer Med.,  2018, 7(12), 6269-6280.
[http://dx.doi.org/10.1002/cam4.1877] [PMID: 30449075] 
[58] 
Wang, Z.; Bhattacharya, A.; Ivanov, D.N. Identification of Small-Molecule Inhibitors of the HuR/RNA Interaction Using a Fluorescence Polarization Screening Assay Followed by NMR Validation. PLoS One,  2015, 10(9)e0138780
[http://dx.doi.org/10.1371/journal.pone.0138780] [PMID: 26390015] 
[59] 
Wu, X.; Lan, L.; Wilson, D.M.; Marquez, R.T.; Tsao, W.C.; Gao, P.; Roy, A.; Turner, B.A.; McDonald, P.; Tunge, J.A.; Rogers, S.A.; Dixon, D.A.; Aubé, J.; Xu, L. Identification and validation of novel small molecule disruptors of HuR-mRNA interaction. ACS Chem. Biol.,  2015, 10(6), 1476-1484.
[http://dx.doi.org/10.1021/cb500851u] [PMID: 25750985] 
[60] 
Sun, D.Q.; Wang, Y.; Liu, D.G. Cancer cell growth suppression by a 62nt AU-rich RNA from C/EBPβ 3'UTR through competitive binding with HuR. Biochem. Biophys. Res. Commun.,  2012, 426(1), 122-128.
[http://dx.doi.org/10.1016/j.bbrc.2012.08.049] [PMID: 22921787] 
[61] 
Manzoni, L.; Zucal, C.; Maio, D.D.; D’Agostino, V.G.; Thongon, N.; Bonomo, I.; Lal, P.; Miceli, M.; Baj, V.; Brambilla, M.; Cerofolini, L.; Elezgarai, S.; Biasini, E.; Luchinat, C.; Novellino, E.; Fragai, M.; Marinelli, L.; Provenzani, A.; Seneci, P. Interfering with HuR-RNA Interaction: Design, synthesis and biological characterization of tanshinone mimics as novel, effective hur inhibitors. J. Med. Chem.,  2018, 61(4), 1483-1498.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01176] [PMID: 29313684] 
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DOI https://dx.doi.org/10.2174/0929867328666210628143430	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

HuR as Therapeutic Target in Cancer: What the Future Holds

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