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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

UBE2L6 is Involved in Cisplatin Resistance by Regulating the Transcription of ABCB6

Author(s): Midori Murakami, Hiroto Izumi*, Tomoko Kurita, Chiho Koi, Yasuo Morimoto and Kiyoshi Yoshino

Volume 20, Issue 12, 2020

Page: [1487 - 1496] Pages: 10

DOI: 10.2174/1871520620666200424130934

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Abstract

Background: Cisplatin is an important anticancer agent in cancer chemotherapy, but when resistant cells appear, treatment becomes difficult, and the prognosis is poor.

Objective: In this study, we investigated the gene expression profile in cisplatin sensitive and resistant cells, and identified the genes involved in cisplatin resistance.

Methods: Comparison of gene expression profiles revealed that UBE2L6 mRNA is highly expressed in resistant cells. To elucidate whether UBE2L6 is involved in the acquisition of cisplatin resistance, UBE2L6- overexpressing cells established from cisplatin-sensitive cells and UBE2L6-silenced cells developed from cisplatin- resistant cells were generated, and the sensitivity of cisplatin was examined.

Results: The sensitivity of the UBE2L6-overexpressing cells did not change compared with the control cells, but the UBE2L6-silenced cells were sensitized to cisplatin. To elucidate the mechanism of UBE2L6 in cisplatin resistance, we compared the gene expression profiles of UBE2L6-silenced cells and control cells and found that the level of ABCB6 mRNA involved in cisplatin resistance was decreased. Moreover, ABCB6 promoter activity was partially suppressed in UBE2L6-silenced cells.

Conclusion: These results suggest that cisplatin-resistant cells have upregulated UBE2L6 expression and contribute to cisplatin resistance by regulating ABCB6 expression at the transcriptional level. UBE2L6 might be a molecular target that overcomes cisplatin resistance.

Keywords: Cisplatin resistance, ubiquitin-proteasome, ISGylation, ABC transporter, cervical cancer cells, transcription.

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[1]
Fitzmaurice, C.; Akinyemiju, T.F.; Al Lami, F.H.; Alam, T.; Alizadeh-Navaei, R.; Allen, C.; Alsharif, U.; Alvis-Guzman, N.; Amini, E.; Anderson, B.O.; Aremu, O.; Artaman, A.; Asgedom, S.W.; Assadi, R.; Atey, T.M.; Avila-Burgos, L.; Awasthi, A.; Ba Saleem, H.O.; Barac, A.; Bennett, J.R.; Bensenor, I.M.; Bhakta, N.; Brenner, H.; Cahuana-Hurtado, L.; Castañeda-Orjuela, C.A.; Catalá-López, F.; Choi, J.J.; Christopher, D.J.; Chung, S.C.; Curado, M.P.; Dandona, L.; Dandona, R. das Neves, J.; Dey, S.; Dharmaratne, S.D.; Doku, D.T.; Driscoll, T.R.; Dubey, M.; Ebrahimi, H.; Edessa, D.; El-Khatib, Z.; Endries, A.Y.; Fischer, F.; Force, L.M.; Foreman, K.J.; Gebrehiwot, S.W.; Gopalani, S.V.; Grosso, G.; Gupta, R.; Gyawali, B.; Hamadeh, R.R.; Hamidi, S.; Harvey, J.; Hassen, H.Y.; Hay, R.J.; Hay, S.I.; Heibati, B.; Hiluf, M.K.; Horita, N.; Hosgood, H.D.; Ilesanmi, O.S.; Innos, K.; Islami, F.; Jakovljevic, M.B.; Johnson, S.C.; Jonas, J.B.; Kasaeian, A.; Kassa, T.D.; Khader, Y.S.; Khan, E.A.; Khan, G.; Khang, Y.H.; Khosravi, M.H.; Khubchandani, J.; Kopec, J.A.; Kumar, G.A.; Kutz, M.; Lad, D.P.; Lafranconi, A.; Lan, Q.; Legesse, Y.; Leigh, J.; Linn, S.; Lunevicius, R.; Majeed, A.; Malekzadeh, R.; Malta, D.C.; Mantovani, L.G.; McMahon, B.J.; Meier, T.; Melaku, Y.A.; Melku, M.; Memiah, P.; Mendoza, W.; Meretoja, T.J.; Mezgebe, H.B.; Miller, T.R.; Mohammed, S.; Mokdad, A.H.; Moosazadeh, M.; Moraga, P.; Mousavi, S.M.; Nangia, V.; Nguyen, C.T.; Nong, V.M.; Ogbo, F.A.; Olagunju, A.T.; Pa, M.; Park, E.K.; Patel, T.; Pereira, D.M.; Pishgar, F.; Postma, M.J.; Pourmalek, F.; Qorbani, M.; Rafay, A.; Rawaf, S.; Rawaf, D.L.; Roshandel, G.; Safiri, S.; Salimzadeh, H.; Sanabria, J.R.; Santric Milicevic, M.M.; Sartorius, B.; Satpathy, M.; Sepanlou, S.G.; Shackelford, K.A.; Shaikh, M.A.; Sharif-Alhoseini, M.; She, J.; Shin, M.J.; Shiue, I.; Shrime, M.G.; Sinke, A.H.; Sisay, M.; Sligar, A.; Sufiyan, M.B.; Sykes, B.L.; Tabarés-Seisdedos, R.; Tessema, G.A.; Topor-Madry, R.; Tran, T.T.; Tran, B.X.; Ukwaja, K.N.; Vlassov, V.V.; Vollset, S.E.; Weiderpass, E.; Williams, H.C.; Yimer, N.B.; Yonemoto, N.; Younis, M.Z.; Murray, C.J.L.; Naghavi, M. Global Burden of Disease Cancer Collaboration. Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 29 cancer groups, 1990 to 2016: A systematic analysis for the global burden of disease study. JAMA Oncol., 2018, 4(11), 1553-1568.
[http://dx.doi.org/10.1001/jamaoncol.2018.2706] [PMID: 29860482]
[2]
Kalemkerian, GP.; Loo, BW.; Akerley, W.; Attia, A.; Bassetti, M.; Boumber, Y.; Decker, R.; Dobelbower, MC.; Dowlati, A.; Downey, RJ.; Florsheim, C.; Ganti, AKP.; Grecula, JC.; Gubens, MA.; Hann, CL.; Hayman, JA.; Heist, RS.; Koczywas, M.; Merritt, RE.; Mohindra, N.; Molina, J.; Moran, CA.; Morgensztern, D.; Pokharel, S.; Portnoy, DC.; Rhodes, D.; Rusthoven, C.; Sands, J.; Santana-Davila, R.; Williams, CC.; Hoffmann, KG.; Hughes, M. NCCN Guidelines Insights: Small Cell Lung Cancer, Version 2.2018. J. Natl. Compr. Canc. Netw., 2018, 16(10), 1171-1182.
[http://dx.doi.org/10.6004/jnccn.2018.0079.]] [PMID: 30323087.]
[3]
Koizumi, W.; Narahara, H.; Hara, T.; Takagane, A.; Akiya, T.; Takagi, M.; Miyashita, K.; Nishizaki, T.; Kobayashi, O.; Takiyama, W.; Toh, Y.; Nagaie, T.; Takagi, S.; Yamamura, Y.; Yanaoka, K.; Orita, H.; Takeuchi, M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): A phase III trial. Lancet Oncol., 2008, 9(3), 215-221.
[http://dx.doi.org/10.1016/S1470-2045(08)70035-4] [PMID: 18282805]
[4]
Cohen, P.A.; Jhingran, A.; Oaknin, A.; Denny, L. Cervical cancer. Lancet, 2019, 393(10167), 169-182.
[http://dx.doi.org/10.1016/S0140-6736(18)32470-X] [PMID: 30638582]
[5]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin., 2019, 69(1), 7-34.
[http://dx.doi.org/10.3322/caac.21551] [PMID: 30620402]
[6]
Zhu, H.; Luo, H.; Zhang, W.; Shen, Z.; Hu, X.; Zhu, X. Molecular mechanisms of cisplatin resistance in cervical cancer. Drug Des. Devel. Ther., 2016, 10, 1885-1895.
[http://dx.doi.org/10.2147/DDDT.S106412] [PMID: 27354763]
[7]
Galluzzi, L.; Senovilla, L.; Vitale, I.; Michels, J.; Martins, I.; Kepp, O.; Castedo, M.; Kroemer, G. Molecular mechanisms of cisplatin resistance. Oncogene, 2012, 31(15), 1869-1883.
[http://dx.doi.org/10.1038/onc.2011.384] [PMID: 21892204]
[8]
Chen, Z.; Shi, T.; Zhang, L.; Zhu, P.; Deng, M.; Huang, C.; Hu, T.; Jiang, L.; Li, J. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett., 2016, 370(1), 153-164.
[http://dx.doi.org/10.1016/j.canlet.2015.10.010] [PMID: 26499806]
[9]
Boswell-Casteel, R.C.; Fukuda, Y.; Schuetz, J.D. ABCB6, an ABC transporter impacting drug response and disease. AAPS J., 2018, 20, 8.
[http://dx.doi.org/10.1208/s12248-017-0165-6] [PMID: 29192381]
[10]
Kelter, G.; Steinbach, D.; Konkimalla, V.B.; Tahara, T.; Taketani, S.; Fiebig, H.H.; Efferth, T. Role of transferrin receptor and the ABC transporters ABCB6 and ABCB7 for resistance and differentiation of tumor cells towards artesunate. PLoS One, 2007, 2(8), e798.
[http://dx.doi.org/10.1371/journal.pone.0000798] [PMID: 17726528]
[11]
Minami, K.; Kamijo, Y.; Nishizawa, Y.; Tabata, S.; Horikuchi, F.; Yamamoto, M.; Kawahara, K.; Shinsato, Y.; Tachiwada, T.; Chen, Z.S.; Tsujikawa, K.; Nakagawa, M.; Seki, N.; Akiyama, S.; Arima, K.; Takeda, Y.; Furukawa, T. Expression of ABCB6 is related to resistance to 5-FU, SN-38 and vincristine. Anticancer Res., 2014, 34(9), 4767-4773.
[PMID: 25202056]
[12]
Nandi, D.; Tahiliani, P.; Kumar, A.; Chandu, D. The ubiquitin proteasome system. J. Biosci., 2006, 31(1), 137-155.
[http://dx.doi.org/10.1007/BF02705243] [PMID: 16595883]
[13]
Liu, J.; Shaik, S.; Dai, X.; Wu, Q.; Zhou, X.; Wang, Z.; Wei, W. Targeting the ubiquitin pathway for cancer treatment. BBA - Rev Cancer, 2015, 1855(1), 50-60.
[14]
Vriend, J.; Reiter, R.J. Breast cancer cells: Modulation by melatonin and the ubiquitin-proteasome system--a review. Mol. Cell. Endocrinol., 2015, 417, 1-9.
[http://dx.doi.org/10.1016/j.mce.2015.09.001] [PMID: 26363225]
[15]
Koi, C.; Izumi, H.; Kurita, T.; Nguyen, T.T.; Murakami, M.; Yoshiura, Y.; Hachisuga, T.; Morimoto, Y. Lovastatin induced Kruppel like factor 2 (KLF2), Kruppel like factor 6 (KLF6) and Ras homolog family member B (RHOB) genes and preferentially led to viability reduction of Cisplatin-resistant cells. Oncotarget, 2017, 8(63), 106429-106442.
[http://dx.doi.org/10.18632/oncotarget.22472] [PMID: 29290960]
[16]
Akiyama, M.; Izumi, H.; Wang, K-Y.; Yamaguchi, T.; Kuma, A.; Kitamura, N.; Harada, Y.; Oya, R.; Yamaguchi, K.; Iwai, Y.; Kohno, K. Hypersensitivity to aurora kinase inhibitors in cells resistant against platinum- containing anticancer agents. Anticancer. Agents Med. Chem., 2014, 14(7), 1042-1050.
[http://dx.doi.org/10.2174/1871520614666140207154351] [PMID: 24521151]
[17]
Sakai, S.; Izumi, H.; Yoshiura, Y.; Nakayama, Y.; Yamaguchi, T.; Harada, Y.; Koi, C.; Kurata, H.; Morimoto, Y. In vitro evaluation of a combination treatment involving anticancer agents and an aurora kinase B inhibitor. Oncol. Lett., 2016, 12(5), 4263-4269.
[http://dx.doi.org/10.3892/ol.2016.5156] [PMID: 27895801]
[18]
Yamaguchi, T.; Kurita, T.; Nishio, K.; Tsukada, J.; Hachisuga, T.; Morimoto, Y.; Iwai, Y.; Izumi, H. Expression of BAF57 in ovarian cancer cells and drug sensitivity. Cancer Sci., 2015, 106(4), 359-366.
[http://dx.doi.org/10.1111/cas.12612]] [PMID: 25611552]
[19]
Chen, S.H.; Chang, J.Y. New Insights into mechanisms of cisplatin resistance: From tumor cell to microenvironment. Int. J. Mol. Sci., 2019, 20(17), 4136.
[http://dx.doi.org/10.3390/ijms20174136] [PMID: 31450627]
[20]
Cocetta, V.; Ragazzi, E.; Montopoli, M. Mitochondrial involvement in cisplatin resistance. Int. J. Mol. Sci., 2019, 20(14), 3384.
[http://dx.doi.org/10.3390/ijms20143384] [PMID: 31295873]
[21]
Rocha, C.R.R.; Silva, M.M.; Quinet, A.; Cabral-Neto, J.B.; Menck, C.F.M. DNA repair pathways and cisplatin resistance: an intimate relationship. Clinics (São Paulo), 2018, 73(Suppl. 1), e478s.
[http://dx.doi.org/10.6061/clinics/2018/e478s] [PMID: 30208165]
[22]
Chen, R.H.; Du, Y.; Han, P.; Wang, H.B.; Liang, F.Y.; Feng, G.K.; Zhou, A.J.; Cai, M.Y.; Zhong, Q.; Zeng, M.S.; Huang, X.M. ISG15 predicts poor prognosis and promotes cancer stem cell phenotype in nasopharyngeal carcinoma. Oncotarget, 2016, 7(13), 16910-16922.
[http://dx.doi.org/10.18632/oncotarget.7626]] [PMID: 26919245]
[23]
Zhou, X.; Wei, J.; Chen, F.; Xiao, X.; Huang, T.; He, Q.; Wang, S.; Du, C.; Mo, Y.; Lin, L.; Xie, Y.; Wei, L.; Lan, Y.; Murata, M.; Huang, G.; Ernberg, I.; Matskova, L.; Zhang, Z. Epigenetic downregulation of the ISG15-conjugating enzyme UbcH8 impairs lipolysis and correlates with poor prognosis in nasopharyngeal carcinoma. Oncotarget, 2015, 6(38), 41077-41091.
[http://dx.doi.org/10.18632/oncotarget.6218] [PMID: 26506425]
[24]
Vtorushin, S.V.; Khristenko, K.Y.; Zavyalova, M.V.; Perelmuter, V.M.; Litviakov, N.V.; Denisov, E.V.; Dulesova, A.Y.; Cherdyntseva, N.V. The phenomenon of multi-drug resistance in the treatment of malignant tumors. Exp. Oncol., 2014, 36(3), 144-156.
[PMID: 25265346]
[25]
Robey, R.W.; Pluchino, K.M.; Hall, M.D.; Fojo, A.T.; Bates, S.E.; Gottesman, M.M. Revisiting the role of ABC transporters in multidrug-resistant cancer. Nat. Rev. Cancer, 2018, 18(7), 452-464.
[http://dx.doi.org/10.1038/s41568-018-0005-8] [PMID: 29643473]
[26]
Yasui, K.; Mihara, S.; Zhao, C.; Okamoto, H.; Saito-Ohara, F.; Tomida, A.; Funato, T.; Yokomizo, A.; Naito, S.; Imoto, I.; Tsuruo, T.; Inazawa, J. Alteration in copy numbers of genes as a mechanism for acquired drug resistance. Cancer Res., 2004, 64(4), 1403-1410.
[http://dx.doi.org/10.1158/0008-5472.CAN-3263-2] [PMID: 14973057]
[27]
Villarroya-Beltri, C.; Guerra, S.; Sánchez-Madrid, F. ISGylation - a key to lock the cell gates for preventing the spread of threats. J. Cell Sci., 2017, 130(18), 2961-2969.
[http://dx.doi.org/10.1242/jcs.205468] [PMID: 28842471]
[28]
Park, J.H.; Yang, S.W.; Park, J.M.; Ka, S.H.; Kim, J.H.; Kong, Y.Y.; Jeon, Y.J.; Seol, J.H.; Chung, C.H. Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification. Nat. Commun., 2016, 7, 12513.
[http://dx.doi.org/10.1038/ncomms12513] [PMID: 27545325]
[29]
Mohammed, Y.I.; Hussam, S.; Mustafa, A. Urolithin A induces prostate cancer cell death in P53 dependent and in P53 independent manner. Eur. J. Nutr., 2020, 59(4), 1607-1618.
[30]
Jeon, Y.J.; Jo, M.G.; Yoo, H.M.; Hong, S.H.; Park, J.M.; Ka, S.H.; Oh, K.H.; Seol, J.H.; Jung, Y.K.; Chung, C.H. Chemosensitivity is controlled by p63 modification with ubiquitin-like protein ISG15. J. Clin. Invest., 2012, 122(7), 2622-2636.
[http://dx.doi.org/10.1172/JCI61762] [PMID: 22706304]
[31]
Huo, Y.; Zong, Z.; Wang, Q.; Zhang, Z.; Deng, H. ISG15 silencing increases cisplatin resistance via activating p53-mediated cell DNA repair. Oncotarget, 2017, 8(64), 107452-107461.
[http://dx.doi.org/10.18632/oncotarget.22488] [PMID: 29296177]
[32]
Falvey, C.M.; O’Donovan, T.R.; El-Mashed, S.; Nyhan, M.J.; O’Reilly, S.; McKenna, S.L. UBE2L6/UBCH8 and ISG15 attenuate autophagy in esophageal cancer cells. Oncotarget, 2017, 8(14), 23479-23491.
[http://dx.doi.org/10.18632/oncotarget.15182] [PMID: 28186990]

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