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

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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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