Aging (Albany NY). 2024 Mar 5;16(5):4631-4653.doi: 10.18632/aging.205618. Epub 2024 Mar 5.

本文采用的英格恩产品: RNA-Entranster-invivo

miR-26a-5p inhibits the proliferation of psoriasis-like keratinocytes in vitro and in vivo by dual interference with the CDC6/CCNE1 axis

Affiliations

Affiliations

  • 1 Key Lab for Zoonoses Research, Ministry of Education, College of Animal Sciences, Jilin University, Changchun 130062, China.
  • 2 Chongqing Research Institute, Jilin University, Chongqing 401123, China.
  • 3 Chongqing Jitang Biotechnology Research Institute Co., Ltd., Chongqing 401123, China.
  • 4 Joint International Research Laboratory of Reproduction and Development, School of Basic Medicine, Chong-qing Medical University, Chongqing 400016, China.
  • 5 Department of Dermatology and Venerology, First Bethune Hospital of Jilin University, Changchun 130021, China.

Abstract

Psoriasis is a chronic inflammatory proliferative dermatological ailment that currently lacks a definitive cure. Employing data mining techniques, this study identified a collection of substantially downregulated miRNAs (top 10). Notably, 32 targets were implicated in both the activation of the IL-17 signaling pathway and cell cycle dysregulation. In silico analysis revealed that one of these miRNAs, miR-26a-5p, is a highly conserved cross-species miRNA. Strikingly, the miR-26a-5p sequences in humans and mice are identical, and mmu-miR-26a-5p was found to target the same 7 cell cycle targets as its human counterpart, hsa-miR-26a-5p. Among these targets, CDC6 and CCNE1 were the most effective targets of miR-26a-5p, which was further validated in vitro using a dual luciferase reporter system and qPCR assay. The therapeutic assessment of miR-26a-5p revealed its remarkable efficacy in inhibiting the proliferation and G1/S transition of keratinocytes (HaCaT and HEKs) in vitro. In vivo experiments corroborated these findings, demonstrating that miR-26a-5p effectively suppressed imiquimod (IMQ)-induced psoriasis-like skin lesions in mice over an 8-day treatment period. Histological analysis via H&E staining revealed that miR-26a-5p treatment resulted in reduced keratinocyte thickness and immune cell infiltration into the spleens of IMQ-treated mice. Mechanistic investigations revealed that miR-26a-5p induced a cascade of downregulated genes associated with the IL-23/IL-17A axis, which is known to be critical in psoriasis pathogenesis, while concomitantly suppressing CDC6 and CCNE1 expression. These findings were corroborated by qPCR and Western blot analyses. Collectively, our study provides compelling evidence supporting the therapeutic potential of miR-26a-5p as a safe and reliable endogenous small nucleic acid for the treatment of psoriasis.

Keywords: CCNE1; CDC6; HEKs; HaCaT cells; imiquimod; miR-26a-5p; miRNA; psoriasis.

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