Inhibition of NRF2 transcription factor mediated by MIR-155 diminishes melanoma cell viability independently of redox status

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Abstract

Redox-sensitive NRF2 transcription factor is a target gene of microRNA miR-155. miR-155 mimic was transfected in dacarbazine-resistant melanoma cells. NRF2 expression levels were down-regulated in miR-155-overexpressed cells independently of oxidative stress induced by hydrogen peroxide. NRF2 suppression was associated with a decrease of melanoma cells viability. As a result, miR-155-mediated NRF2 overexpression that regulate intensity of a cell antioxidant processes can be associated with cancer cell survival leading to drug resistance. NRF2 repression by miR-155 highlighted a potential for NRF2 down-regulation as an approach in anticancer therapy.

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About the authors

V. A. Kutsenko

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: tatyana_ruksha@mail.ru
Russian Federation, Krasnoyarsk

D. A. Dashkova

Voino-Yasenetsky Krasnoyarsk State Medical University

Email: tatyana_ruksha@mail.ru
Russian Federation, Krasnoyarsk

T. G. Ruksha

Voino-Yasenetsky Krasnoyarsk State Medical University

Author for correspondence.
Email: tatyana_ruksha@mail.ru
Russian Federation, Krasnoyarsk

References

  1. Лапкина Е.З., Есимбекова А.Р., Беленюк В.Д., Савченко А.А., Рукша Т.Г. 2022. Распределение клеток меланомы В16 по фазам клеточного цикла под воздействием дакарбазина. Цитология. Т. 64. № 6. С. 573. (Lapkina E.Z., Esimbekova A.R., Beleniuk V.D., Savchenko A.A., Ruksha T.G. 2023. The distribution of B16 melanoma cells in cell-cycle phases under the influence of dacarbazine. Cell Tiss. Biol. V. 17. P. 161.)
  2. Aksenenko M.B., Palkina N.V., Sergeeva O.N., Sergeeva Yu.E., Kirichenko A.K., Ruksha T.G. 2019. miR-155 overexpression is followed by downregulation of its target gene, NFE2L2, and altered pattern of VEGFA expression in the liver of melanoma B16-bearing mice at the premetastatic stage. Int. J. Exp. Pathol. V. 100. P. 311.
  3. Aramouni K., Assaf R., Shaito A., Fardoun M., Al-Asmakh M., Sahebkar A., Eid A.H. 2023. Biochemical and cellular basis of oxidative stress: Implications for disease onset. J. Cell Physiol. V. 238. P. 1951. https://doi.org/ 10.1002/jcp.31071
  4. Bollong M.J., Lee G., Coukos J.S., Yun H., Zambaldo C., Chang J.W., Chin E.N., Ahmad I., Chatterjee A.K., Lairson L.L., Schultz P.G., Moellering R.E. 2018. A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling. Nature. V. 562. P. 600. https://doi.org/10.1038/s41586-018-0622-0
  5. Camiña N., Penning T.M. 2022. Genetic and epigenetic regulation of the NRF2-KEAP1 pathway in human lung cancer. Br. J. Cancer. V. 126. P. 1244. https://doi.org/10.1038/s41416-021-01642-0
  6. Cheung E.C., Vousden K.H. 2022. The role of ROS in tumour development and progression. Nat. Rev. Cancer. V. 22. P. 280. https://doi.org/ 10.1038/s41568-021-00435-0
  7. DiSano J.A., Huffnagle I., Gowda R., Spiegelman V.S., Robertson G.P., Pameijer C.R. 2019. Loss of miR-155 upregulates WEE1 in metastatic melanoma. Melanoma Res. V. 29. P. 216. https://doi.org/10.1097/CMR.0000000000000545
  8. Esimbekova A.R., Palkina N.V., Zinchenko I.S., Belenyuk V.D., Savchenko A.A., Sergeeva E.Y., Ruksha T.G. 2023. Focal adhesion alterations in G0-positive melanoma cells. Cancer Med. V. 12. P. 7294. https://doi.org/10.1002/cam4.5510
  9. Fan Z., Wirth A.K., Chen D., Wruck C.J., Rauh M., Buchfelder M., Savaskan N. 2017. Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis. Oncogenesis. V. 6. P. 371. https://doi.org/10.1038/oncsis.2017.65
  10. Feng Q., Xu X., Zhang S. 2023. Nrf2 protein in melanoma progression, as a new means of treatment. Pigment Cell Melanoma Res. https://doi.org/10.1111/pcmr.13137
  11. Han Y., Gao X., Wu N., Jin Y., Zhou H., Wang W., Liu H., Chu Y., Cao J., Jiang M., Yang S., Shi Y., Xie X., Chen F., Han Y., et al., 2022. Long noncoding RNA LINC00239 inhibits ferroptosis in colorectal cancer by binding to Keap1 to stabilize Nrf2. Cell Death Dis. V. 13. P. 742. https://doi.org/10.1038/s41419-022-05192-y
  12. Knatko E.V., Castro C., Higgins M., Zhang Y., Honda T., Henderson C.J., Wolf C.R., Griffin J.L., Dinkova-Kostova A.T. 2021. Nrf2 activation does not affect adenoma development in a mouse model of colorectal cancer. Commun. Biol. V. 4. P. 1081. https://doi.org/10.1038/s42003-021-02552-w
  13. Komina A.V., Korostileva K.A., Gyrylova S.N., Belonogov R.N., Ruksha T.G. 2012. Interaction between single nucleotide polymorphism in catalase gene and catalase activity under the conditions of oxidative stress. Physiol. Res. V. 61. P. 655. https://doi.org/10.33549/physiolres.932333
  14. Li H., Song J.B., Chen H.X., Wang Q.Q., Meng L.X., Li Y. 2019. MiR-155 inhibits proliferation, invasion and migration of melanoma via targeting CBL. Eur. Rev. Med. Pharmacol. Sci. V. 23. P. 9525. https://doi.org/10.26355/eurrev_201911_19447
  15. Liu G., He L., Yang X., Tang L., Shi W., She J., Wei J. 2023. MicroRNA-155-5p aggravates adriamycin-induced focal segmental glomerulosclerosis through targeting Nrf2. Nephron. V. 147. P. 108. https://doi.org/10.1159/000525233
  16. Milkovic L., Zarkovic N., Saso L. 2017. Controversy about pharmacological modulation of Nrf2 for cancer therapy. Redox Biol. V. 12. P. 727. https://doi.org/10.1016/j.redox.2017.04.013
  17. Seddon A.R., Das A.B., Hampton M.B., Stevens A.J. Site-specific decreases in DNA methylation in replicating cells following exposure to oxidative stress. Hum. Mol. Genet. 2023. V. 32. P. 632. https://doi.org/0.1093/hmg/ddac232
  18. Tossetta G., Marzioni D. 2023. Targeting the NRF2/KEAP1 pathway in cervical and endometrial cancers. Eur. J. Pharmacol. V. 941. P. 175503. https://doi.org/10.1016/j.ejphar.2023.175503
  19. Wang J. Sun Y., Zhang X., Cai H., Zhang C., Qu H., Liu L., Zhang M., Fu J., Zhang J., Wang J., Zhang G. 2021. Oxidative stress activates NORAD expression by H3K27ac and promotes oxaliplatin resistance in gastric cancer by enhancing autophagy flux via targeting the miR-433-3p. Cell Death Dis. V. 12. P. 90. https://doi.org/10.1038/s41419-020-03368-y
  20. Wu J., Minikes A.M., Gao M., Bian H., Li Y., Stockwell B.R., Chen Z.N., Jiang X. 2019. Intercellular interaction dictates cancer cell ferroptosis via NF2-YAP signalling. 2019. Nature. V. 572. P. 402. https://doi.org/10.1038/s41586-019-1426-6

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2. Fig. 1. Expression levels of miR-155 microRNA in B16 melanoma cells after the action of 0.1% DMSO, 1.2 mM dacarbazine, dacarbazine followed by transfection of miR-155 mimic negative control, dacarbazine followed by transfection of miR-155 microRNA mimetic before oxidative stress (a) and 24 h after addition of 700 μM H2O2 (b). According to PCR-RV results; (*) - differences are reliable at P = 0.0495 (Kraskell-Wallace test)

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3. Fig. 2. Expression levels of NFE2L2, encoding the NRF2 transcription factor, in B16 melanoma cells exposed to DMSO, dacarabazine, dacarbazine followed by transfection of negative control, dacarabazine followed by transfection of miR-155 microRNA mimetic in the absence of H2O2 (a) and after addition of 700 μM H2O2 (b). (*) - P = 0.0495 (Kraskell-Wallace test)

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4. Fig. 3. Viability of B16 melanoma cells exposed to DMSO, dacarabazine, dacarbazine followed by transfection of negative control, dacarabazine followed by transfection of miR-155 microRNA mimetic in the absence of H2O2 (a) and after addition of 700 μM H2O2 (b). Evaluation of the optical density of the reaction product in the MTT assay. (*) - P = 0.0495 (Kraskell-Wallace test)

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5. Fig. 4. Culture of melanoma cell line B16 after exposure to DMSO (a), dacarbazine (b), dacarbazine followed by transfection of negative control (c), dacarbazine followed by transfection of miR-155 microRNA mimetic (d) in absence conditions (a-d) and after addition of 700 μM H2O2 in the same groups (f-h)

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