Upregulation of MicroRNA-144 Suppresses Nrf2 Antioxidant Signaling Pathway in Patients with Severe COVID-19

Mahdieh Nasirzadeh; Mahdi Pouramir; Shiva Gholizadeh-Ghaleh Aziz; Shahriar Alipour

doi:10.18502/ijaai.v24i1.18018

Mahdieh Nasirzadeh Department of Clinical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
Mahdi Pouramir Department of Clinical Biochemistry, Faculty of Medicine, Babol University of Medical Sciences, Babol, Iran
Shiva Gholizadeh-Ghaleh Aziz Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran
Shahriar Alipour Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran

DOI: https://doi.org/10.18502/ijaai.v24i1.18018

Keywords: COVID-19; MIR153-1; MIR144; Nrf2 Signaling pathway

Abstract

MicroRNAs (miRs) play a pivotal role in the pathogenesis of viral infections. It has been proven that the Nrf2 (NFE2 like bZIP transcription factor 2) antioxidant signaling pathway is inhibited in COVID-19 patients. Two microRNAs (MIR144 and MIR153-1) have been identified as important Nrf2 regulators. The aim of this study was to analyze the MIR144 and MIR153-1 expression in COVID-19 patients and investigate their association with the Nrf2 signaling pathway.

The study had 82 participants with both mild and severe COVID-19 manifestations and 25 healthy as a control group. Ficoll density-gradient centrifugation was used to separate peripheral blood mononuclear cells from ethylenediaminetetraacetic acid blood tubes. MIR144, MIR153-1, and NFE2L2 expressions were studied using real-time polymerase chain reaction. We employed the commercially available enzyme-linked immunosorbent assay to measure plasma Nrf2 protein concentration and the activity of antioxidant enzymes, superoxide dismutase, and catalase.

Compared to the control group, MIR144 expression was significantly increased in the severe group, while NFE2L2 expression decreased. There was no significant difference in the MIR153-1 expression rate between COVID-19 patients and controls. Nrf2 protein and antioxidant enzyme activity significantly decreased in the severe group. A negative correlation between MIR144 expression and Nrf2 protein concentration was observed.

Taken together, the current study's findings showed that MIR144 upregulation probably interferes with the Nrf2 antioxidant signaling pathway in COVID-19 patients.