A circular RNA, circPTPN14, increases MYC transcription by interacting with FUBP1 and exacerbates renal fibrosis.

Abstract

Fibrosis is a relentlessly progressive and irreversible cause of organ damage, as in chronic kidney disease (CKD), but its underlying mechanisms remain elusive. We found that a circular RNA, circPTPN14, is highly expressed in human kidneys with biopsy-proved chronic interstitial fibrosis, mouse kidneys subjected to ischemia/reperfusion (IR) or unilateral ureteral obstruction (UUO), and TGFβ1-stimulated renal tubule epithelial cells (TECs). The intrarenal injection of circPTPN14 shRNA alleviated the progression of fibrosis in kidneys subjected to IR or UUO. Knockdown of circPTPN14 in TECs inhibited TGFβ1-induced expression of profibrotic genes, whereas overexpressing circPTPN14 increased the profibrotic effect of TGFβ1. The profibrotic action of circPTPN14 was ascribed to an increase in MYC transcription. The binding of circPTPN14 to the KH3 and KH4 domains of far upstream element (FUSE) binding protein 1 (FUBP1) enhanced the interaction between FUBP1 and FUSE domain, which was required for the initiation of MYC transcription. In human kidneys (n = 30) with biopsy-proved chronic interstitial fibrosis, the expression of circPTPN14 positively correlated with MYC expression. Taken together these studies show a novel mechanism in the pathogenesis of renal fibrosis, mediated by circPTPN14, which can be a target in the diagnosis and treatment of CKD.

• Authors: Wanyun Nie, Mobai Li, Boqiang Liu, Ying Zhang, Yuxi Wang, Junni Wang, Lini Jin, Anqi Ni, Liang Xiao, Xiao Z Shen, Jianghua Chen, Weiqiang Lin, Fei Han
• Journal: Cellular and molecular life sciences : CMLS (Cell Mol Life Sci) Vol. 79 Issue 12 Pg. 595 (Nov 17 2022) ISSN: 1420-9071 [Electronic] Switzerland
• PMID: 36394649 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• DNA-Binding Proteins
• FUBP1 protein, human
• Proto-Oncogene Proteins c-myc
• RNA, Circular
• RNA-Binding Proteins

Topics

• Animals
• Humans
• Mice
• DNA-Binding Proteins (genetics, metabolism)
• Fibrosis
• Kidney (metabolism)
• Proto-Oncogene Proteins c-myc
• Renal Insufficiency, Chronic (pathology)
• RNA, Circular (genetics)
• RNA-Binding Proteins (genetics, metabolism)
• Ureteral Obstruction (genetics, metabolism, pathology)
• Transcription, Genetic