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

作者全名:"Li, Jianing; Pang, Daxin; Zhou, Lin; Ouyang, Hongsheng; Tian, Yaping; Yu, Hao"

作者地址:"[Li, Jianing; Pang, Daxin; Ouyang, Hongsheng; Yu, Hao] Jilin Univ, Coll Anim Sci, Key Lab Zoonoses Res, Minist Educ, Changchun 130062, Peoples R China; [Pang, Daxin; Ouyang, Hongsheng] Jilin Univ, Chongqing Res Inst, Chongqing 401123, Peoples R China; [Pang, Daxin; Ouyang, Hongsheng] Chongqing Jitang Biotechnol Res Inst Co Ltd, Chongqing 401123, Peoples R China; [Zhou, Lin] Chongqing Med Univ, Sch Basic Med, Joint Int Res Lab Reprod & Dev, Chongqing 400016, Peoples R China; [Tian, Yaping] Jilin Univ, Dept Dermatol & Venerol, Bethune Hosp 1, Changchun 130021, Peoples R China"

通信作者:"Yu, H (通讯作者),Jilin Univ, Coll Anim Sci, Key Lab Zoonoses Res, Minist Educ, Changchun 130062, Peoples R China.; Tian, YP (通讯作者),Jilin Univ, Dept Dermatol & Venerol, Bethune Hosp 1, Changchun 130021, Peoples R China."

来源:AGING-US

ESI学科分类:MOLECULAR BIOLOGY & GENETICS

WOS号:WOS:001188188200018

JCR分区:Q2

影响因子:3.9

年份:2024

卷号:16

期号:5

开始页:4631

结束页:4653

文献类型:Article

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

摘要:"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 crossspecies 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 miR26a-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."

基金机构:Jilin Province Science and Technology Development Plan Project [20190201049JC]

基金资助正文:<BOLD> </BOLD> This study was financially supported by the Jilin Province Science and Technology Development Plan Project (20190201049JC) awarded to Prof. Yaping Tian.