Circ_0024390 promotes renal tubular EMT through the miR-6890-3p/CHD4 axis: implications for renal interstitial fibrosis
Year: 2026
Type: article
Abstract: Background: Renal interstitial fibrosis (RIF) is a central pathological event in the progression of various chronic kidney diseases (CKD) to end-stage renal disease, for which effective therapeutic strategies remain lacking. Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells serves as a pivotal mechanism driving RIF. While circular RNAs (circRNAs) have been implicated in various pathological processes, their specific roles and underlying mechanisms in the progression of RIF remain incompletely elucidated. Methods: A circRNA microarray was utilized to screen differentially expressed circRNAs in a TGF-β1-induced HK-2 cell model of renal fibrosis. Loss-of-function experiments were performed to explore the biological effects of circ_0024390 on renal tubular EMT, as well as the proliferation and migration of HK-2 cells. Mechanistic assays were further conducted to verify the competing endogenous RNA (ceRNA) regulatory mechanism of circ_0024390. Results: Circ_0024390 was significantly upregulated in the in vitro fibrosis model, specifically in TGF-β1-induced HK-2 cells. Functional studies demonstrated that knockdown of circ_0024390 effectively attenuated renal tubular EMT and inhibited key cellular processes, including proliferation and migration. Mechanistic investigations further revealed that circ_0024390 functioned as a ceRNA by sponging miR-6890-3p. This sponging relieved the repressive effect of miR-6890-3p on its downstream target, chromodomain helicase DNA-binding protein 4 (CHD4), leading to the upregulation of CHD4 expression. Conclusion: These findings delineate a novel circ_0024390/miR-6890-3p/CHD4 axis that promotes EMT in renal tubular epithelial cells and contributes to the progression of RIF. This study provides new insights into the pathogenesis of RIF and highlights circ_0024390 as a potential promising therapeutic target for CKD.
Source: Frontiers in Pharmacology
Authors: Xue Yang, Lujie Zhang, Yan Song, Gang Liu
Institutions: Shandong University, Qilu Hospital of Shandong University
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G3904361112
OpenAlex ID: W7221747963
