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Cell Physiol Biochem. 2018;49(6):2174-2187. doi: 10.1159/000493821. Epub 2018 Sep 26.

Long Non-Coding RNA CYP4B1-PS1-001 Inhibits Proliferation and Fibrosis in Diabetic Nephropathy by Interacting with Nucleolin.

Author information

1
Department of Endocrinology and Metabolism, Huai'an First People's Hospital, Nanjing Medical University, Jiangsu, China.
2
Department of Microbiology, Nanjing Medical University, Nanjing, China.

Abstract

BACKGROUND/AIMS:

Our previous studies demonstrated that a novel long non-coding RNA, CYP4B1-PS1-001, was significantly downregulated in early diabetic nephropathy in vivo and in vitro, and CYP4B1-PS1-001 overexpression could inhibit the proliferation and fibrosis of mouse mesangial cells (MMCs). However, the underlying mechanism of the CYP4B1-PS1-001-mediated regulation of proliferation and fibrosis in diabetic nephropathy remains undetermined.

METHODS:

RNA-protein pull-down assay, RNA-binding protein immunoprecipitation, and mass spectrometry were used to investigate CYP4B1-PS1-001 interacted with the upregulated protein nucleolin (NCL). siRNA method was applied to knockdown NCL in MMCs, the interaction between CYP4B1-PS1-001 and NCL were determined by Western blot analysis and RT-qPCR. The effect of CYP4B1-PS1-001 in the regulation of NCL was detected by cycloheximide (CHX) and ubiquitination assays.

RESULTS:

We found that CYP4B1-PS1-001 interacts with NCL, and CYP4B1-PS1-001 inhibits the proliferation and fibrosis of MMCs depending on interaction with NCL. Furthermore, degradation of CYP4B1-PS1-001-associated NCL was mediated by a ubiquitin proteasome-dependent pathway.

CONCLUSION:

Our study provides evidence that CYP4B1-PS1-001 regulates the ubiquitination and degradation of NCL and thereby plays a critical role in the proliferation and fibrosis of MMCs, indicating that CYP4B1-PS1-001 and NCL may be promising prognostic biomarkers and molecular targets for the treatment of diabetic nephropathy.

KEYWORDS:

Diabetic nephropathy; Fibrosis; LncRNA; Nucleolin; Proliferation; Ubiquitination

PMID:
30257240
DOI:
10.1159/000493821
[Indexed for MEDLINE]
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