MicroRNA-mediated Redox Regulation Modulates Therapy Resistance in Cancer Cells: Clinical Perspectives

Overview

Journal Cell Oncol (Dordr)

Publisher Springer

Date 2019 Jan 16

PMID 30645730

Citations 17

Authors

Safieh Ebrahimi

Seyed Isaac Hashemy

Affiliations

Soon will be listed here.

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.

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References

Li L, Story M, Legerski R . Cellular responses to ionizing radiation damage. Int J Radiat Oncol Biol Phys. 2001; 49(4):1157-62. DOI: 10.1016/s0360-3016(00)01524-8. View

Khanna K, Jackson S . DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet. 2001; 27(3):247-54. DOI: 10.1038/85798. View

Silber J, Bobola M, Blank A, Schoeler K, Haroldson P, Huynh M . 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. 2002; 8(9):3008-18. View

Izumi T, Wiederhold L, Roy G, Roy R, Jaiswal A, Bhakat K . Mammalian DNA base excision repair proteins: their interactions and role in repair of oxidative DNA damage. Toxicology. 2003; 193(1-2):43-65. DOI: 10.1016/s0300-483x(03)00289-0. View

Klaunig J, Kamendulis L . The role of oxidative stress in carcinogenesis. Annu Rev Pharmacol Toxicol. 2004; 44:239-67. DOI: 10.1146/annurev.pharmtox.44.101802.121851. View

Bartel D . MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004; 116(2):281-97. DOI: 10.1016/s0092-8674(04)00045-5. View

Kuhne M, Riballo E, Rief N, Rothkamm K, Jeggo P, Lobrich M . A double-strand break repair defect in ATM-deficient cells contributes to radiosensitivity. Cancer Res. 2004; 64(2):500-8. DOI: 10.1158/0008-5472.can-03-2384. View

Conklin K . Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integr Cancer Ther. 2004; 3(4):294-300. DOI: 10.1177/1534735404270335. View

Longley D, Johnston P . Molecular mechanisms of drug resistance. J Pathol. 2005; 205(2):275-92. DOI: 10.1002/path.1706. View

10.

Kobayashi M, Yamamoto M . Molecular mechanisms activating the Nrf2-Keap1 pathway of antioxidant gene regulation. Antioxid Redox Signal. 2005; 7(3-4):385-94. DOI: 10.1089/ars.2005.7.385. View

11.

Dean M, Fojo T, Bates S . Tumour stem cells and drug resistance. Nat Rev Cancer. 2005; 5(4):275-84. DOI: 10.1038/nrc1590. View

12.

Kondo Y, Kanzawa T, Sawaya R, Kondo S . The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 2005; 5(9):726-34. DOI: 10.1038/nrc1692. View

13.

Ramanathan B, Jan K, Chen C, Hour T, Yu H, Pu Y . Resistance to paclitaxel is proportional to cellular total antioxidant capacity. Cancer Res. 2005; 65(18):8455-60. DOI: 10.1158/0008-5472.CAN-05-1162. View

14.

Hashemy S, Ungerstedt J, Avval F, Holmgren A . Motexafin gadolinium, a tumor-selective drug targeting thioredoxin reductase and ribonucleotide reductase. J Biol Chem. 2006; 281(16):10691-7. DOI: 10.1074/jbc.M511373200. View

15.

Pervaiz S, Clement M . Superoxide anion: oncogenic reactive oxygen species?. Int J Biochem Cell Biol. 2007; 39(7-8):1297-304. DOI: 10.1016/j.biocel.2007.04.007. View

16.

Ailles L, Weissman I . Cancer stem cells in solid tumors. Curr Opin Biotechnol. 2007; 18(5):460-6. DOI: 10.1016/j.copbio.2007.10.007. View

17.

Josson S, Sung S, Lao K, Chung L, Johnstone P . Radiation modulation of microRNA in prostate cancer cell lines. Prostate. 2008; 68(15):1599-606. PMC: 3182144. DOI: 10.1002/pros.20827. View

18.

Ogasawara M, Zhang H . Redox regulation and its emerging roles in stem cells and stem-like cancer cells. Antioxid Redox Signal. 2008; 11(5):1107-22. DOI: 10.1089/ars.2008.2308. View

19.

Diehn M, Cho R, Lobo N, Kalisky T, Dorie M, Kulp A . Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009; 458(7239):780-3. PMC: 2778612. DOI: 10.1038/nature07733. View

20.

Hayes J, McMahon M . NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci. 2009; 34(4):176-88. DOI: 10.1016/j.tibs.2008.12.008. View