MicroRNA-mediated redox regulation modulates therapy resistance in cancer cells: clinical perspectives
Abstract
Background
Chemotherapy and radiation therapy are the most common types of cancer therapy. The development of chemo/radio-resistance remains, however, a major obstacle. Altered redox balances are among of the main factors mediating therapy resistance. Therefore, redox regulatory strategies are urgently needed to overcome this problem. Recently, microRNAs have been found to act as major redox regulatory factors affecting chemo/radio-resistance. MicroRNAs play critical roles in regulating therapeutic resistance through the regulation of antioxidant enzymes, redox-sensitive signaling pathways, cancer stem cells, DNA repair mechanisms and autophagy.
Conclusions
Here, we summarize current knowledge on microRNA-mediated redox regulatory mechanisms underlying chemo/radio-resistance. This knowledge may form a basis for a better clinical management of cancer patients.
Keywords
Cancer Chemotherapy Radiotherapy Resistance MicroRNA Redox regulationNotes
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
References
- 1.D.B. Longley, P.G. Johnston, Molecular mechanisms of drug resistance. J. Pathol. 205, 275–292 (2005)CrossRefPubMedGoogle Scholar
- 2.F. Perri, R. Pacelli, G. Della Vittoria Scarpati, L. Cella, M. Giuliano, F. Caponigro, S. Pepe, Radioresistance in head and neck squamous cell carcinoma: Biological bases and therapeutic implications. Head Neck 37, 763–770 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
- 3.S.K. Niture, A.K. Jaiswal, Nrf2-induced antiapoptotic Bcl-xL protein enhances cell survival and drug resistance. Free Radic. Biol. Med. 57, 119–131 (2013)CrossRefPubMedGoogle Scholar
- 4.G. Frosina, DNA repair and resistance of gliomas to chemotherapy and radiotherapy. Mol. Cancer Res. 7, 989–999 (2009)CrossRefPubMedGoogle Scholar
- 5.M. Dean, T. Fojo, S. Bates, Tumour stem cells and drug resistance. Nat. Rev. Cancer 5, 275–284 (2005)CrossRefPubMedGoogle Scholar
- 6.S. Chen, S.K. Rehman, W. Zhang, A. Wen, L. Yao, J. Zhang, Autophagy is a therapeutic target in anticancer drug resistance. Biochim. Biophys. Acta (BBA)-Reviews on Cancer 1806, 220–229 (2010)Google Scholar
- 7.S.L. Lomonaco, S. Finniss, C. Xiang, A. Decarvalho, F. Umansky, S.N. Kalkanis, T. Mikkelsen, C. Brodie, The induction of autophagy by gamma-radiation contributes to the radioresistance of glioma stem cells. Int. J. Cancer 125, 717–722 (2009)CrossRefPubMedGoogle Scholar
- 8.V.J. Victorino, L. Pizzatti, P. Michelletti, C. Panis, Oxidative stress, redox signaling and cancer chemoresistance: Putting together the pieces of the puzzle. Curr. Med. Chem. 21, 3211–3226 (2014)CrossRefPubMedGoogle Scholar
- 9.H. Sies, Oxidative stress: Introductory remarks. Oxidative Stress 501, 1–8 (1985)Google Scholar
- 10.H. Sies, E. Cadenas, Oxidative stress: Damage to intact cells and organs. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 311, 617–631 (1985)CrossRefGoogle Scholar
- 11.A. Pakfetrat, Z. Dalirsani, S.I. Hashemy, A. Ghazi, L.V. Mostaan, K. Anvari, A.M. Pour, Evaluation of serum levels of oxidized and reduced glutathione and total antioxidant capacity in patients with head and neck squamous cell carcinoma. J. Cancer Res. Ther. 14, 428–431 (2018)PubMedGoogle Scholar
- 12.S. Lorestani, S.I. Hashemy, M. Mojarad, M. Keyvanloo Shahrestanaki, A. Bahari, M. Asadi, F. Zahedi Avval, Increased glutathione reductase expression and activity in colorectal Cancer tissue samples: An investigational study in Mashhad, Iran. Middle East J. Cancer 9, 99–104 (2018)Google Scholar
- 13.A. Taheri, M.H. Tanipour, Z.K. Khorasani, B. Kiafar, P. Layegh, S.I. Hashemy, Serum protein carbonyl and total antioxidant capacity levels in pemphigus vulgaris and bullous pemphigoid. Iran J. Dermatol. 18, 156–162 (2016)Google Scholar
- 14.M. Sobhani, A.R. Taheri, A.H. Jafarian, S.I. Hashemy, The activity and tissue distribution of thioredoxin reductase in basal cell carcinoma. J. Cancer Res. Clin. 142, 2303–2307 (2016)CrossRefGoogle Scholar
- 15.S.I. Hashemy, S. Gharaei, S. Vasigh, S. Kargozar, B. Alirezaei, F.J. Keyhani, M. Amirchaghmaghi, Oxidative stress factors and C-reactive protein in patients with oral lichen planus before and 2 weeks after treatment. J. Oral Pathol. Med. 45, 35–40 (2016)CrossRefPubMedGoogle Scholar
- 16.M. Amirchaghmaghi, S.I. Hashemy, B. Alirezaei, F. Jahed Keyhani, S. Kargozar, S. Vasigh, S. Gharaei, A. Pakfetrat, Evaluation of plasma Isoprostane in patients with Oral lichen planus. J. Dent. 17, 21–25 (2016)Google Scholar
- 17.P. Sharma, S. Kumar, Metformin inhibits human breast cancer cell growth by promoting apoptosis via a ROS-independent pathway involving mitochondrial dysfunction: Pivotal role of superoxide dismutase (SOD). Cell. Oncol. 41, 637–650 (2018)CrossRefGoogle Scholar
- 18.S. Banskota, S. Dahal, E. Kwon, D.Y. Kim, J.A. Kim, beta-catenin gene promoter hypermethylation by reactive oxygen species correlates with the migratory and invasive potentials of colon cancer cells. Cell. Oncol. 41, 569–580 (2018)CrossRefGoogle Scholar
- 19.L. Li, M. Story, R.J. Legerski, Cellular responses to ionizing radiation damage. Int. J. Radiat. Oncol. Biol. Phys. 49, 1157–1162 (2001)CrossRefPubMedGoogle Scholar
- 20.K.A. Conklin, Chemotherapy-associated oxidative stress: Impact on chemotherapeutic effectiveness. Integr. Cancer Ther. 3, 294–300 (2004)CrossRefPubMedGoogle Scholar
- 21.S.I. Hashemy, J.S. Ungerstedt, F. Zahedi Avval, A. Holmgren, Motexafin gadolinium, a tumor-selective drug targeting thioredoxin reductase and ribonucleotide reductase. J. Biol. Chem. 281, 10691–10697 (2006)CrossRefPubMedGoogle Scholar
- 22.S. Pervaiz, M.V. Clement, Superoxide anion: Oncogenic reactive oxygen species? Int. J. Biochem. Cell Biol. 39, 1297–1304 (2007)CrossRefPubMedGoogle Scholar
- 23.V. Sosa, T. Moline, R. Somoza, R. Paciucci, H. Kondoh, L.L. ME, Oxidative stress and cancer: An overview. Ageing Res. Rev. 12, 376–390 (2013)CrossRefPubMedGoogle Scholar
- 24.S.A. Castaldo, J.R. Freitas, N.V. Conchinha, P.A. Madureira, The tumorigenic roles of the cellular REDOX regulatory systems. Oxidative Med. Cell. Longev. 2016, 8413032 (2016)CrossRefGoogle Scholar
- 25.J.E. Klaunig, L.M. Kamendulis, The role of oxidative stress in carcinogenesis. Annu. Rev. Pharmacol. Toxicol. 44, 239–267 (2004)CrossRefPubMedGoogle Scholar
- 26.D. Trachootham, J. Alexandre, P. Huang, Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat. Rev. Drug Discov. 8, 579–591 (2009)CrossRefPubMedGoogle Scholar
- 27.S.I. Hashemy, The human Thioredoxin system: Modifications and clinical applications. Iran J. Basic Med. Sci. 14, 191–204 (2011)Google Scholar
- 28.A.M. Pisoschi, A. Pop, The role of antioxidants in the chemistry of oxidative stress: A review. Eur. J. Med. Chem. 97, 55–74 (2015)CrossRefPubMedGoogle Scholar
- 29.B. Ramanathan, K.Y. Jan, C.H. Chen, T.C. Hour, H.J. Yu, Y.S. Pu, Resistance to paclitaxel is proportional to cellular total antioxidant capacity. Cancer Res. 65, 8455–8460 (2005)CrossRefPubMedGoogle Scholar
- 30.M. Diehn, R.W. Cho, N.A. Lobo, T. Kalisky, M.J. Dorie, A.N. Kulp, D. Qian, J.S. Lam, L.E. Ailles, M. Wong, B. Joshua, M.J. Kaplan, I. Wapnir, F.M. Dirbas, G. Somlo, C. Garberoglio, B. Paz, J. Shen, S.K. Lau, S.R. Quake, J.M. Brown, I.L. Weissman, M.F. Clarke, Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458, 780–783 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
- 31.M.A. Ogasawara, H. Zhang, Redox regulation and its emerging roles in stem cells and stem-like cancer cells. Antioxid. Redox Signal. 11, 1107–1122 (2009)CrossRefPubMedGoogle Scholar
- 32.J. He, B.H. Jiang, Interplay between reactive oxygen species and MicroRNAs in Cancer. Curr. Pharmacol. Rep. 2, 82–90 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 33.D.P. Bartel, MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 116, 281–297 (2004)CrossRefPubMedGoogle Scholar
- 34.F. Corra, C. Agnoletto, L. Minotti, F. Baldassari, S. Volinia, The network of non-coding RNAs in Cancer drug resistance. Front. Oncol. 8, 327 (2018)CrossRefPubMedPubMedCentralGoogle Scholar
- 35.A.K. Mueller, K. Lindner, R. Hummel, J. Haier, D.I. Watson, D.J. Hussey, MicroRNAs and their impact on radiotherapy for cancer. Radiat. Res. 185, 668–677 (2016)Google Scholar
- 36.G.S. Markopoulos, E. Roupakia, M. Tokamani, E. Chavdoula, M. Hatziapostolou, C. Polytarchou, K.B. Marcu, A.G. Papavassiliou, R. Sandaltzopoulos, E. Kolettas, A step-by-step microRNA guide to cancer development and metastasis. Cell. Oncol. 40, 303–339 (2017)CrossRefGoogle Scholar
- 37.N.L. Simone, B.P. Soule, D. Ly, A.D. Saleh, J.E. Savage, W. Degraff, J. Cook, C.C. Harris, D. Gius, J.B. Mitchell, Ionizing radiation-induced oxidative stress alters miRNA expression. PLoS One 4, e6377 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
- 38.T. Templin, S. Paul, S.A. Amundson, E.F. Young, C.A. Barker, S.L. Wolden, L.B. Smilenov, Radiation-induced micro-RNA expression changes in peripheral blood cells of radiotherapy patients. Int. J. Radiat. Oncol. Biol. Phys. 80, 549–557 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
- 39.J. Lin, C.C. Chuang, L. Zuo, Potential roles of microRNAs and ROS in colorectal cancer: Diagnostic biomarkers and therapeutic targets. Oncotarget 8, 17328–17346 (2017)PubMedPubMedCentralGoogle Scholar
- 40.M. Kobayashi, M. Yamamoto, Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid. Redox Signal. 7, 385–394 (2005)CrossRefPubMedGoogle Scholar
- 41.J.D. Hayes, M. McMahon, NRF2 and KEAP1 mutations: Permanent activation of an adaptive response in cancer. Trends Biochem. Sci. 34, 176–188 (2009)CrossRefPubMedGoogle Scholar
- 42.L. Zhao, M. Tang, Z. Hu, B. Yan, W. Pi, Z. Li, J. Zhang, L. Zhang, W. Jiang, G. Li, Y. Qiu, F. Hu, F. Liu, J. Lu, X. Chen, L. Xiao, Z. Xu, Y. Tao, L. Yang, A.M. Bode, Z. Dong, J. Zhou, J. Fan, L. Sun, Y. Cao, miR-504 mediated down-regulation of nuclear respiratory factor 1 leads to radio-resistance in nasopharyngeal carcinoma. Oncotarget 6, 15995–16018 (2015)PubMedPubMedCentralGoogle Scholar
- 43.L. Shi, L. Wu, Z. Chen, J. Yang, X. Chen, F. Yu, F. Zheng, X. Lin, MiR-141 activates Nrf2-dependent antioxidant pathway via Down-regulating the expression of Keap1 conferring the resistance of hepatocellular carcinoma cells to 5-fluorouracil. Cell. Physiol. Biochem. 35, 2333–2348 (2015)CrossRefPubMedGoogle Scholar
- 44.S. Zhou, W. Ye, Y. Zhang, D. Yu, Q. Shao, J. Liang, M. Zhang, miR-144 reverses chemoresistance of hepatocellular carcinoma cell lines by targeting Nrf2-dependent antioxidant pathway. Am. J. Transl. Res. 8, 2992–3002 (2016)Google Scholar
- 45.L. Shi, Z.G. Chen, L.L. Wu, J.J. Zheng, J.R. Yang, X.F. Chen, Z.Q. Chen, C.L. Liu, S.Y. Chi, J.Y. Zheng, H.X. Huang, X.Y. Lin, F. Zheng, miR-340 reverses cisplatin resistance of hepatocellular carcinoma cell lines by targeting Nrf2-dependent antioxidant pathway. Asian Pac. J. Cancer Prev. 15, 10439–10444 (2014)CrossRefPubMedGoogle Scholar
- 46.S.E. Gomes, D.M. Pereira, C. Roma-Rodrigues, A.R. Fernandes, P.M. Borralho, C.M.P. Rodrigues, Convergence of miR-143 overexpression, oxidative stress and cell death in HCT116 human colon cancer cells. PLoS One 13, e0191607 (2018)CrossRefPubMedPubMedCentralGoogle Scholar
- 47.Y. Cui, K. She, D. Tian, P. Zhang, X. Xin, miR-146a inhibits proliferation and enhances Chemosensitivity in epithelial ovarian Cancer via reduction of SOD2. Oncol. Res. 23, 275–282 (2016)CrossRefPubMedGoogle Scholar
- 48.M.A. Cortez, D. Valdecanas, X. Zhang, Y. Zhan, V. Bhardwaj, G.A. Calin, R. Komaki, D.K. Giri, C.C. Quini, T. Wolfe, H.J. Peltier, A.G. Bader, J.V. Heymach, R.E. Meyn, J.W. Welsh, Therapeutic delivery of miR-200c enhances radiosensitivity in lung cancer. Mol. Ther. 22, 1494–1503 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
- 49.C. Gao, F.H. Peng, L.K. Peng, MiR-200c sensitizes clear-cell renal cell carcinoma cells to sorafenib and imatinib by targeting heme oxygenase-1. Neoplasma 61, 680–689 (2014)CrossRefPubMedGoogle Scholar
- 50.H.C. Chen, Y.M. Jeng, R.H. Yuan, H.C. Hsu, Y.L. Chen, SIRT1 promotes tumorigenesis and resistance to chemotherapy in hepatocellular carcinoma and its expression predicts poor prognosis. Ann. Surg. Oncol. 19, 2011–2019 (2012)CrossRefPubMedGoogle Scholar
- 51.A. Salminen, K. Kaarniranta, A. Kauppinen, Crosstalk between oxidative stress and SIRT1: Impact on the aging process. Int. J. Mol. Sci. 14, 3834–3859 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
- 52.M. Chang, L. Qiao, B. Li, J. Wang, G. Zhang, W. Shi, Z. Liu, N. Gu, Z. Di, X. Wang, Y. Tian, Suppression of SIRT6 by miR-33a facilitates tumor growth of glioma through apoptosis and oxidative stress resistance. Oncol. Rep. 38, 1251–1258 (2017)CrossRefPubMedGoogle Scholar
- 53.H. Liu, X.H. Cheng, MiR-29b reverses oxaliplatin-resistance in colorectal cancer by targeting SIRT1. Oncotarget 9, 12304–12315 (2018)PubMedPubMedCentralGoogle Scholar
- 54.B. Lian, D. Yang, Y. Liu, G. Shi, J. Li, X. Yan, K. Jin, X. Liu, J. Zhao, W. Shang, R. Zhang, miR-128 targets the SIRT1/ROS/DR5 pathway to sensitize colorectal Cancer to TRAIL-induced apoptosis. Cell. Physiol. Biochem. 49, 2151–2162 (2018)CrossRefPubMedGoogle Scholar
- 55.X. Xu, A. Wells, M.T. Padilla, K. Kato, K.C. Kim, Y. Lin, A signaling pathway consisting of miR-551b, catalase and MUC1 contributes to acquired apoptosis resistance and chemoresistance. Carcinogenesis 35, 2457–2466 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
- 56.Z. Dong, L. Ren, L. Lin, J. Li, Y. Huang, J. Li, Effect of microRNA-21 on multidrug resistance reversal in A549/DDP human lung cancer cells. Mol. Med. Rep. 11, 682–690 (2015)CrossRefPubMedGoogle Scholar
- 57.C. Lin, L. Xie, Y. Lu, Z. Hu, J. Chang, miR-133b reverses cisplatin resistance by targeting GSTP1 in cisplatin-resistant lung cancer cells. Int. J. Mol. Med. 41, 2050–2058 (2018)PubMedPubMedCentralGoogle Scholar
- 58.S. Chen, J.W. Jiao, K.X. Sun, Z.H. Zong, Y. Zhao, MicroRNA-133b targets glutathione S-transferase pi expression to increase ovarian cancer cell sensitivity to chemotherapy drugs. Drug Des. Devel. Ther. 9, 5225–5235 (2015)PubMedPubMedCentralGoogle Scholar
- 59.D. Wang, N. Zhang, Y. Ye, J. Qian, Y. Zhu, C. Wang, Role and mechanisms of microRNA-503 in drug resistance reversal in HepG2/ADM human hepatocellular carcinoma cells. Mol. Med. Rep. 10, 3268–3274 (2014)CrossRefPubMedGoogle Scholar
- 60.G.K. Patel, M.A. Khan, A. Bhardwaj, S.K. Srivastava, H. Zubair, M.C. Patton, S. Singh, M. Khushman, A.P. Singh, Exosomes confer chemoresistance to pancreatic cancer cells by promoting ROS detoxification and miR-155-mediated suppression of key gemcitabine-metabolising enzyme, DCK. Br. J. Cancer 116, 609–619 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
- 61.L.E. Ailles, I.L. Weissman, Cancer stem cells in solid tumors. Curr. Opin. Biotechnol. 18, 460–466 (2007)CrossRefPubMedGoogle Scholar
- 62.H.Q. Ju, Y.X. Lu, D.L. Chen, T. Tian, H.Y. Mo, X.L. Wei, J.W. Liao, F. Wang, Z.L. Zeng, H. Pelicano, M. Aguilar, W.H. Jia, R.H. Xu, Redox regulation of stem-like cells though the CD44v-xCT Axis in colorectal Cancer: Mechanisms and therapeutic implications. Theranostics 6, 1160–1175 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 63.B. Mateescu, L. Batista, M. Cardon, T. Gruosso, Y. de Feraudy, O. Mariani, A. Nicolas, J.P. Meyniel, P. Cottu, X. Sastre-Garau, F. Mechta-Grigoriou, miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response. Nat. Med. 17, 1627–1635 (2011)CrossRefPubMedGoogle Scholar
- 64.W. Yang, Y. Shen, J. Wei, F. Liu, MicroRNA-153/Nrf-2/GPx1 pathway regulates radiosensitivity and stemness of glioma stem cells via reactive oxygen species. Oncotarget 6, 22006–22027 (2015)PubMedPubMedCentralGoogle Scholar
- 65.S. Venkataraman, I. Alimova, R. Fan, P. Harris, N. Foreman, R. Vibhakar, MicroRNA 128a increases intracellular ROS level by targeting Bmi-1 and inhibits medulloblastoma cancer cell growth by promoting senescence. PLoS One 5, e10748 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
- 66.X. Sun, Y. Li, M. Zheng, W. Zuo, W. Zheng, MicroRNA-223 increases the sensitivity of triple-negative breast Cancer stem cells to TRAIL-induced apoptosis by targeting HAX-1. PLoS One 11, e0162754 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 67.J. Liu, Q. Tang, S. Li, X. Yang, Inhibition of HAX-1 by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells. Oncotarget 7, 86446–86456 (2016)PubMedPubMedCentralGoogle Scholar
- 68.K.K. Khanna, S.P. Jackson, DNA double-strand breaks: Signaling, repair and the cancer connection. Nat. Genet. 27, 247–254 (2001)CrossRefPubMedGoogle Scholar
- 69.S.P. Jackson, J. Bartek, The DNA-damage response in human biology and disease. Nature 461, 1071–1078 (2009)CrossRefPubMedPubMedCentralGoogle Scholar
- 70.M. Kuhne, E. Riballo, N. Rief, K. Rothkamm, P.A. Jeggo, M. Lobrich, A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res. 64, 500–508 (2004)CrossRefPubMedGoogle Scholar
- 71.M. Pajic, D. Froio, S. Daly, L. Doculara, E. Millar, P.H. Graham, A. Drury, A. Steinmann, C.E. de Bock, A. Boulghourjian, A. Zaratzian, S. Carroll, J. Toohey, S.A. O'Toole, A.L. Harris, F.M. Buffa, H.E. Gee, G.E. Hollway, T.J. Molloy, miR-139-5p modulates radiotherapy resistance in breast Cancer by repressing multiple gene networks of DNA repair and ROS defense. Cancer Res. 78, 501–515 (2018)CrossRefPubMedGoogle Scholar
- 72.H. Hu, X. Zhao, Z. Jin, M. Hou, Hsa-let-7g miRNA regulates the anti-tumor effects of gastric cancer cells under oxidative stress through the expression of DDR genes. J. Toxicol. Sci. 40, 329–338 (2015)CrossRefPubMedGoogle Scholar
- 73.D. Yan, W.L. Ng, X. Zhang, P. Wang, Z. Zhang, Y.Y. Mo, H. Mao, C. Hao, J.J. Olson, W.J. Curran, Y. Wang, Targeting DNA-PKcs and ATM with miR-101 sensitizes tumors to radiation. PLoS One 5, e11397 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
- 74.H. Hu, L. Du, G. Nagabayashi, R.C. Seeger, R.A. Gatti, ATM is down-regulated by N-Myc-regulated microRNA-421. Proc. Natl. Acad. Sci. U. S. A. 107, 1506–1511 (2010)CrossRefPubMedPubMedCentralGoogle Scholar
- 75.J. Wang, J. He, F. Su, N. Ding, W. Hu, B. Yao, W. Wang, G. Zhou, Repression of ATR pathway by miR-185 enhances radiation-induced apoptosis and proliferation inhibition. Cell Death Dis. 4, e699 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
- 76.L. Song, C. Lin, Z. Wu, H. Gong, Y. Zeng, J. Wu, M. Li, J. Li, miR-18a impairs DNA damage response through downregulation of ataxia telangiectasia mutated (ATM) kinase. PLoS One 6, e25454 (2011)CrossRefPubMedPubMedCentralGoogle Scholar
- 77.A. Cataldo, D.G. Cheung, A. Balsari, E. Tagliabue, V. Coppola, M.V. Iorio, D. Palmieri, C.M. Croce, miR-302b enhances breast cancer cell sensitivity to cisplatin by regulating E2F1 and the cellular DNA damage response. Oncotarget 7, 786–797 (2016)CrossRefPubMedGoogle Scholar
- 78.S. Xu, H. Huang, Y.N. Chen, Y.T. Deng, B. Zhang, X.D. Xiong, Y. Yuan, Y. Zhu, H. Huang, L. Xie, X. Liu, DNA damage responsive miR-33b-3p promoted lung cancer cells survival and cisplatin resistance by targeting p21(WAF1/CIP1). Cell Cycle 15, 2920–2930 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 79.P. Carotenuto, D. Zito, M.C. Previdi, M. Raj, M. Fassan, A. Lampis, F. Scalafani, A. Lanese, I. Said-Huntingford and J.C. Hahne, (AACR, 2018)Google Scholar
- 80.A. Besse, J. Sana, R. Lakomy, L. Kren, P. Fadrus, M. Smrcka, M. Hermanova, R. Jancalek, S. Reguli, R. Lipina, M. Svoboda, P. Slampa, O. Slaby, MiR-338-5p sensitizes glioblastoma cells to radiation through regulation of genes involved in DNA damage response. Tumour. Biol. 37, 7719–7727 (2016)CrossRefPubMedGoogle Scholar
- 81.R.L. Liu, Y. Dong, Y.Z. Deng, W.J. Wang, W.D. Li, Tumor suppressor miR-145 reverses drug resistance by directly targeting DNA damage-related gene RAD18 in colorectal cancer. Tumour. Biol. 36, 5011–5019 (2015)CrossRefPubMedGoogle Scholar
- 82.Y.N. Shen, I.S. Bae, G.H. Park, H.S. Choi, K.H. Lee, S.H. Kim, MicroRNA-196b enhances the radiosensitivity of SNU-638 gastric cancer cells by targeting RAD23B. Biomed. Pharmacother. 105, 362–369 (2018)CrossRefPubMedGoogle Scholar
- 83.M. Xiao, J. Cai, L. Cai, J. Jia, L. Xie, Y. Zhu, B. Huang, D. Jin, Z. Wang, Let-7e sensitizes epithelial ovarian cancer to cisplatin through repressing DNA double strand break repair. J. Ovarian Res. 10, 24 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
- 84.T.H. Lai, B. Ewald, A. Zecevic, C. Liu, M. Sulda, D. Papaioannou, R. Garzon, J.S. Blachly, W. Plunkett, D. Sampath, HDAC inhibition induces MicroRNA-182, which targets RAD51 and impairs HR repair to sensitize cells to Sapacitabine in acute myelogenous leukemia. Clin. Cancer Res. 22, 3537–3549 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 85.Y. Wang, J.W. Huang, P. Calses, C.J. Kemp, T. Taniguchi, MiR-96 downregulates REV1 and RAD51 to promote cellular sensitivity to cisplatin and PARP inhibition. Cancer Res. 72, 4037–4046 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
- 86.J.W. Huang, Y. Wang, K.K. Dhillon, P. Calses, E. Villegas, P.S. Mitchell, M. Tewari, C.J. Kemp, T. Taniguchi, Systematic screen identifies miRNAs that target RAD51 and RAD51D to enhance chemosensitivity. Mol. Cancer Res. 11, 1564–1573 (2013)CrossRefPubMedGoogle Scholar
- 87.P. Gasparini, F. Lovat, M. Fassan, L. Casadei, L. Cascione, N.K. Jacob, S. Carasi, D. Palmieri, S. Costinean, C.L. Shapiro, K. Huebner, C.M. Croce, Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation. Proc. Natl. Acad. Sci. U. S. A. 111, 4536–4541 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
- 88.G. Antoniali, F. Serra, L. Lirussi, M. Tanaka, C. D'Ambrosio, S. Zhang, S. Radovic, E. Dalla, Y. Ciani, A. Scaloni, M. Li, S. Piazza, G. Tell, Mammalian APE1 controls miRNA processing and its interactome is linked to cancer RNA metabolism. Nat. Commun. 8, 797 (2017)CrossRefPubMedPubMedCentralGoogle Scholar
- 89.D. Ramotar, A. Nepveu, Apurinic/apyrimidinic endonuclease 1 performs multiple roles in controlling the outcome of cancer cells toward radiation and chemotherapeutic agents. J. Rad. Cancer Res. 9, 67 (2018)CrossRefGoogle Scholar
- 90.J.R. Silber, M.S. Bobola, A. Blank, K.D. Schoeler, P.D. Haroldson, M.B. Huynh, D.D. Kolstoe, The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin. Cancer Res. 8, 3008–3018 (2002)PubMedGoogle Scholar
- 91.H. Chen, X. Li, W. Li, H. Zheng, miR-130a can predict response to temozolomide in patients with glioblastoma multiforme, independently of O6-methylguanine-DNA methyltransferase. J. Transl. Med. 13, 69 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
- 92.L. Tinaburri, M. D'Errico, S. Sileno, R. Maurelli, P. Degan, A. Magenta, E. Dellambra, miR-200a modulates the expression of the DNA repair protein OGG1 playing a role in aging of primary human keratinocytes. Oxidative Med. Cell. Longev. 2018, 9147326 (2018)CrossRefGoogle Scholar
- 93.T. Izumi, L.R. Wiederhold, G. Roy, R. Roy, A. Jaiswal, K.K. Bhakat, S. Mitra, T.K. Hazra, Mammalian DNA base excision repair proteins: Their interactions and role in repair of oxidative DNA damage. Toxicology 193, 43–65 (2003)CrossRefPubMedGoogle Scholar
- 94.H.L. Huang, Y.P. Shi, H.J. He, Y.H. Wang, T. Chen, L.W. Yang, T. Yang, J. Chen, J. Cao, W.M. Yao, G. Liu, MiR-4673 modulates paclitaxel-induced oxidative stress and loss of mitochondrial membrane potential by targeting 8-Oxoguanine-DNA Glycosylase-1. Cell. Physiol. Biochem. 42, 889–900 (2017)CrossRefPubMedGoogle Scholar
- 95.Y.T. Gao, X.B. Chen, H.L. Liu, Up-regulation of miR-370-3p restores glioblastoma multiforme sensitivity to temozolomide by influencing MGMT expression. Sci. Rep. 6, 32972 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 96.S. Josson, S.Y. Sung, K. Lao, L.W. Chung, P.A. Johnstone, Radiation modulation of microRNA in prostate cancer cell lines. Prostate 68, 1599–1606 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
- 97.N.M. Mazure, J. Pouyssegur, Hypoxia-induced autophagy: Cell death or cell survival? Curr. Opin. Cell. Biol. 22, 177–180 (2010)CrossRefPubMedGoogle Scholar
- 98.J. Lee, S. Giordano, J. Zhang, Autophagy, mitochondria and oxidative stress: Cross-talk and redox signalling. Biochem. J. 441, 523–540 (2012)CrossRefPubMedGoogle Scholar
- 99.Y. Kondo, T. Kanzawa, R. Sawaya, S. Kondo, The role of autophagy in cancer development and response to therapy. Nat. Rev. Cancer 5, 726–734 (2005)CrossRefPubMedGoogle Scholar
- 100.A.C. Gurkan, E.D. Arisan, P.O. Yerlikaya, H. Ilhan, N.P. Unsal, Inhibition of autophagy enhances DENSpm-induced apoptosis in human colon cancer cells in a p53 independent manner. Cell. Oncol. 41, 297–317 (2018)CrossRefGoogle Scholar
- 101.W. Khaodee, N. Inboot, S. Udomsom, W. Kumsaiyai, R. Cressey, Glucosidase II beta subunit (GluIIbeta) plays a role in autophagy and apoptosis regulation in lung carcinoma cells in a p53-dependent manner. Cell. Oncol. 40, 579–591 (2017)Google Scholar
- 102.X. Sui, R. Chen, Z. Wang, Z. Huang, N. Kong, M. Zhang, W. Han, F. Lou, J. Yang, Q. Zhang, X. Wang, C. He, H. Pan, Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment. Cell Death Dis. 4, e838 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
- 103.A. Chatterjee, D. Chattopadhyay, G. Chakrabarti, miR-17-5p downregulation contributes to paclitaxel resistance of lung cancer cells through altering beclin1 expression. PLoS One 9, e95716 (2014)CrossRefPubMedPubMedCentralGoogle Scholar
- 104.X. Wu, X. Feng, X. Zhao, F. Ma, N. Liu, H. Guo, C. Li, H. Du, B. Zhang, Role of Beclin-1-mediated autophagy in the survival of pediatric leukemia cells. Cell. Physiol. Biochem. 39, 1827–1836 (2016)CrossRefPubMedGoogle Scholar
- 105.X. Yang, F. Bai, Y. Xu, Y. Chen, L. Chen, Intensified Beclin-1 mediated by low expression of Mir-30a-5p promotes Chemoresistance in human small cell lung Cancer. Cell. Physiol. Biochem. 43, 1126–1139 (2017)CrossRefPubMedGoogle Scholar
- 106.J. Xu, H. Huang, R. Peng, X. Ding, B. Jiang, X. Yuan, J. Xi, MicroRNA-30a increases the chemosensitivity of U251 glioblastoma cells to temozolomide by directly targeting beclin 1 and inhibiting autophagy. Exp. Ther. Med. 15, 4798–4804 (2018)PubMedPubMedCentralGoogle Scholar
- 107.Y. Zhang, X. Meng, C. Li, Z. Tan, X. Guo, Z. Zhang, T. Xi, MiR-9 enhances the sensitivity of A549 cells to cisplatin by inhibiting autophagy. Biotechnol. Lett. 39, 959–966 (2017)CrossRefPubMedGoogle Scholar
- 108.W. Li, Y. Yang, Z. Ba, S. Li, H. Chen, X. Hou, L. Ma, P. He, L. Jiang, L. Li, R. He, L. Zhang, D. Feng, MicroRNA-93 regulates hypoxia-induced autophagy by targeting ULK1. Oxidative Med. Cell. Longev. 2017, 2709053 (2017)Google Scholar
- 109.S.I. Rothschild, O. Gautschi, J. Batliner, M. Gugger, M.F. Fey, M.P. Tschan, MicroRNA-106a targets autophagy and enhances sensitivity of lung cancer cells to Src inhibitors. Lung Cancer 107, 73–83 (2017)CrossRefPubMedGoogle Scholar
- 110.L. Hua, G. Zhu and J. Wei, MicroRNA-1 overexpression increases chemosensitivity of non-small cell lung cancer cells by inhibiting autophagy related 3-mediated autophagy. Cell. Biol. Int. (2018). https://doi.org/10.1002/cbin.10995
- 111.Y. Xu, Y. An, Y. Wang, C. Zhang, H. Zhang, C. Huang, H. Jiang, X. Wang, X. Li, miR-101 inhibits autophagy and enhances cisplatin-induced apoptosis in hepatocellular carcinoma cells. Oncol. Rep. 29, 2019–2024 (2013)CrossRefPubMedGoogle Scholar
- 112.J. Zhao, Y. Nie, H. Wang, Y. Lin, MiR-181a suppresses autophagy and sensitizes gastric cancer cells to cisplatin. Gene 576, 828–833 (2016)CrossRefPubMedGoogle Scholar
- 113.A.M. Gao, X.Y. Zhang, J.N. Hu, Z.P. Ke, Apigenin sensitizes hepatocellular carcinoma cells to doxorubic through regulating miR-520b/ATG7 axis. Chem. Biol. Interact. 280, 45–50 (2018)CrossRefPubMedGoogle Scholar
- 114.H. Zhang, J. Tang, C. Li, J. Kong, J. Wang, Y. Wu, E. Xu, M. Lai, MiR-22 regulates 5-FU sensitivity by inhibiting autophagy and promoting apoptosis in colorectal cancer cells. Cancer Lett. 356, 781–790 (2015)CrossRefPubMedGoogle Scholar
- 115.J. Xiong, D. Wang, A. Wei, N. Ke, Y. Wang, J. Tang, S. He, W. Hu, X. Liu, MicroRNA-410-3p attenuates gemcitabine resistance in pancreatic ductal adenocarcinoma by inhibiting HMGB1-mediated autophagy. Oncotarget 8, 107500–107512 (2017)PubMedPubMedCentralGoogle Scholar
- 116.W.W. Ren, D.D. Li, X. Chen, X.L. Li, Y.P. He, L.H. Guo, L.N. Liu, L.P. Sun, X.P. Zhang, MicroRNA-125b reverses oxaliplatin resistance in hepatocellular carcinoma by negatively regulating EVA1A mediated autophagy. Cell Death Dis. 9, 547 (2018)CrossRefPubMedPubMedCentralGoogle Scholar
- 117.L. Huang, C. Hu, H. Cao, X. Wu, R. Wang, H. Lu, H. Li, H. Chen, MicroRNA-29c increases the Chemosensitivity of pancreatic Cancer cells by inhibiting USP22 mediated autophagy. Cell. Physiol. Biochem. 47, 747–758 (2018)CrossRefPubMedGoogle Scholar
- 118.P.H. Chen, A.J. Liu, K.H. Ho, Y.T. Chiu, Z.H. Anne Lin, Y.T. Lee, C.M. Shih, K.C. Chen, microRNA-199a/b-5p enhance imatinib efficacy via repressing WNT2 signaling-mediated protective autophagy in imatinib-resistant chronic myeloid leukemia cells. Chem. Biol. Interact. 291, 144–151 (2018)CrossRefPubMedGoogle Scholar
- 119.H. Gu, M. Liu, C. Ding, X. Wang, R. Wang, X. Wu, R. Fan, Hypoxia-responsive miR-124 and miR-144 reduce hypoxia-induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing PIM1. Cancer Med. 5, 1174–1182 (2016)CrossRefPubMedPubMedCentralGoogle Scholar
- 120.P. Wang, J. Zhang, L. Zhang, Z. Zhu, J. Fan, L. Chen, L. Zhuang, J. Luo, H. Chen, L. Liu, Z. Chen, Z. Meng, MicroRNA 23b regulates autophagy associated with radioresistance of pancreatic cancer cells. Gastroenterology 145, 1133–1143 e1112 (2013)CrossRefPubMedGoogle Scholar
- 121.X. Zhang, H. Shi, S. Lin, M. Ba, S. Cui, MicroRNA-216a enhances the radiosensitivity of pancreatic cancer cells by inhibiting beclin-1-mediated autophagy. Oncol. Rep. 34, 1557–1564 (2015)CrossRefPubMedGoogle Scholar
- 122.H. Liao, Y. Xiao, Y. Hu, Y. Xiao, Z. Yin, L. Liu, microRNA-32 induces radioresistance by targeting DAB2IP and regulating autophagy in prostate cancer cells. Oncol. Lett. 10, 2055–2062 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
- 123.J. Luo, J. Chen, L. He, mir-129-5p attenuates irradiation-induced autophagy and decreases radioresistance of breast cancer cells by targeting HMGB1. Med. Sci. Monit. 21, 4122–4129 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
- 124.Q. Sun, T. Liu, Y. Yuan, Z. Guo, G. Xie, S. Du, X. Lin, Z. Xu, M. Liu, W. Wang, Q. Yuan, L. Chen, MiR-200c inhibits autophagy and enhances radiosensitivity in breast cancer cells by targeting UBQLN1. Int. J. Cancer 136, 1003–1012 (2015)CrossRefPubMedGoogle Scholar
- 125.C. Meng, Y. Liu, Y. Shen, S. Liu, Z. Wang, Q. Ye, H. Liu, X. Liu, L. Jia, MicroRNA-26b suppresses autophagy in breast cancer cells by targeting DRAM1 mRNA, and is downregulated by irradiation. Oncol. Lett. 15, 1435–1440 (2018)PubMedGoogle Scholar
- 126.W. Wang, J. Liu, Q. Wu, MiR-205 suppresses autophagy and enhances radiosensitivity of prostate cancer cells by targeting TP53INP1. Eur. Rev. Med. Pharmacol. Sci. 20, 92–100 (2016)PubMedGoogle Scholar
- 127.J. Liu, Y. Xing, L. Rong, miR-181 regulates cisplatin-resistant non-small cell lung cancer via downregulation of autophagy through the PTEN/PI3K/AKT pathway. Oncol. Rep. 39, 1631–1639 (2018)PubMedPubMedCentralGoogle Scholar
- 128.X. Du, B. Liu, X. Luan, Q. Cui, L. Li, miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy. Exp. Ther. Med. 15, 599–605 (2018)PubMedGoogle Scholar
- 129.B. Zheng, H. Zhu, D. Gu, X. Pan, L. Qian, B. Xue, D. Yang, J. Zhou, Y. Shan, MiRNA-30a-mediated autophagy inhibition sensitizes renal cell carcinoma cells to sorafenib. Biochem. Biophys. Res. Commun. 459, 234–239 (2015)CrossRefPubMedGoogle Scholar
- 130.S. Comincini, G. Allavena, S. Palumbo, M. Morini, F. Durando, F. Angeletti, L. Pirtoli, C. Miracco, microRNA-17 regulates the expression of ATG7 and modulates the autophagy process, improving the sensitivity to temozolomide and low-dose ionizing radiation treatments in human glioblastoma cells. Cancer Biol. Ther. 14, 574–586 (2013)CrossRefPubMedPubMedCentralGoogle Scholar
- 131.W. Hou, L. Song, Y. Zhao, Q. Liu, S. Zhang, Inhibition of Beclin-1-mediated autophagy by MicroRNA-17-5p enhanced the Radiosensitivity of glioma cells. Oncol. Res. 25, 43–53 (2017)CrossRefPubMedGoogle Scholar
- 132.H.S. Gwak, T.H. Kim, G.H. Jo, Y.J. Kim, H.J. Kwak, J.H. Kim, J. Yin, H. Yoo, S.H. Lee, J.B. Park, Silencing of microRNA-21 confers radio-sensitivity through inhibition of the PI3K/AKT pathway and enhancing autophagy in malignant glioma cell lines. PLoS One 7, e47449 (2012)CrossRefPubMedPubMedCentralGoogle Scholar
- 133.J.L. Hu, G.Y. He, X.L. Lan, Z.C. Zeng, J. Guan, Y. Ding, X.L. Qian, W.T. Liao, Y.Q. Ding, L. Liang, Inhibition of ATG12-mediated autophagy by miR-214 enhances radiosensitivity in colorectal cancer. Oncogene 7, 16 (2018)CrossRefGoogle Scholar
- 134.Z. Liu, S. Huang, Inhibition of miR-191 contributes to radiation-resistance of two lung cancer cell lines by altering autophagy activity. Cancer Cell. Int. 15, 16 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
- 135.H. Yi, B. Liang, J. Jia, N. Liang, H. Xu, G. Ju, S. Ma, X. Liu, Differential roles of miR-199a-5p in radiation-induced autophagy in breast cancer cells. FEBS Lett. 587, 436–443 (2013)CrossRefPubMedGoogle Scholar
- 136.M.T. van Jaarsveld, J. Helleman, A.W. Boersma, P.F. van Kuijk, W.F. van Ijcken, E. Despierre, I. Vergote, R.H. Mathijssen, E.M. Berns, J. Verweij, J. Pothof, E.A. Wiemer, miR-141 regulates KEAP1 and modulates cisplatin sensitivity in ovarian cancer cells. Oncogene 32, 4284–4293 (2013)CrossRefPubMedGoogle Scholar
- 137.N. Duru, R. Gernapudi, Y. Zhang, Y. Yao, P.K. Lo, B. Wolfson, Q. Zhou, NRF2/miR-140 signaling confers radioprotection to human lung fibroblasts. Cancer Lett. 369, 184–191 (2015)CrossRefPubMedPubMedCentralGoogle Scholar
- 138.M.S. Joo, C.G. Lee, J.H. Koo, S.G. Kim, miR-125b transcriptionally increased by Nrf2 inhibits AhR repressor, which protects kidney from cisplatin-induced injury. Cell Death Dis. e899, 4 (2013)Google Scholar