miR-582-5p targets Skp1 and regulates NF-κB signaling-mediated inflammation.

Archives of biochemistry and biophysics 2023 Jan 15

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A well-tuned inflammatory response is crucial for an effective immune process. Nuclear factor-kappa B (NF-κB) is a key mediator of inflammatory and innate immunity responses, and its dysregulation is closely associated with immune-related diseases. MicroRNAs (miRNAs) are important inflammation modulators. However, miRNA-regulated mechanisms that implicate NF-κB activity are not fully understood. This study aimed to identify a potential miRNA that could modulate the dysregulated NF-κB signaling during inflammation. We identified miR-582-5p that was significantly downregulated in inflamed murine adipose tissues and RAW264.7 cells. S-phase kinase-associated protein 1 (SKP1), a core component of an E3 ubiquitin ligase that regulates the NF-κB pathway, was proposed as a biological target of miR-582-5p by using TargetScan. The binding of miR-582-5p to a 3'-untranslated region site on Skp1 was confirmed using a dual-luciferase reporter assay; in addition, transfection with a miR-582-5p mimic suppressed SKP1 expression in RAW264.7 cells. Importantly, exogenous miR-582-5p attenuated the production of pro-inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 through suppressing the degradation of the NF-κB inhibitor alpha, followed by the nuclear translocation of NF-κB. Therefore, exogenously applied miR-582-5p can attenuate the NF-κB signaling pathway via targeting Skp1; this provides a prospective therapeutic strategy for treating inflammatory and immune diseases. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Rongzhi Li, Tomomi Sano, Akiko Mizokami, Takao Fukuda, Takanori Shinjo, Misaki Iwashita, Akiko Yamashita, Terukazu Sanui, Yusuke Nakatsu, Yusuke Sotomaru, Tomoichiro Asano, Takashi Kanematsu, Fusanori Nishimura. miR-582-5p targets Skp1 and regulates NF-κB signaling-mediated inflammation. Archives of biochemistry and biophysics. 2023 Jan 15;734:109501