Circ_0024390 promotes renal tubular EMT through the miR-6890-3p/CHD4 axis: implications for renal interstitial fibrosis
- 1Department of Nephrology, Multidisciplinary Innovation Center for Nephrology, The Second Qilu Hospital of Shandong University
- 2Nephrology Research Institute of Shandong University
- 3Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University
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.
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BibTeX
@article{yang2026circ0024390,
title = {{Circ_0024390 promotes renal tubular EMT through the miR-6890-3p/CHD4 axis: implications for renal interstitial fibrosis}},
author = {Xue Yang and Lujie Zhang and Yan Song and Gang Liu},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1941987},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1941987/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Circ_0024390 promotes renal tubular EMT through the miR-6890-3p/CHD4 axis: implications for renal interstitial fibrosis
AU - Xue Yang
AU - Lujie Zhang
AU - Yan Song
AU - Gang Liu
PY - 2026
DA - 2026/10/14
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1941987
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1941987/full
AB - 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.
SN - 1663-9812
ER -