Back to Search Start Over

LncRNA NEAT1 Promotes High Glucose-Induced Mesangial Cell Hypertrophy by Targeting miR-222-3p/CDKN1B Axis

Authors :
Lin Liao
Jie Chen
Chuanfu Zhang
Yue Guo
Weiwei Liu
Wenrui Liu
Lianxiang Duan
Ziyang Liu
Jing Hu
Jianrao Lu
Source :
Frontiers in Molecular Biosciences, Vol 7 (2021)
Publication Year :
2021
Publisher :
Frontiers Media S.A., 2021.

Abstract

Glomerular hypertrophy is an early morphological alteration in diabetic nephropathy. Cyclin-Dependent Kinases have been shown to be required for high glucose (HG)-induced hypertrophy; however, the upstream regulators of CDKN1B in glomerular hypertrophy remain unclear. Herein we describe a novel pathway in which Long noncoding RNA (lncRNA) NEAT1 regulates the progression of mesangial cell hypertrophy via a competing endogenous RNA (ceRNA) mechanism. Real-time PCR was performed to detect the relative NEAT1 and miR-222-3p expressions and further confirmed the relationship between NEAT1 and miR-222-3p. Cell cycle was evaluated by flow cytometry. The related mechanisms were explored by Western blot, RNA immunoprecipitation and chromatin immunoprecipitation assay. We show that NEAT1 forms double stranded RNA (dsRNA) with miR-222-3p, thus limiting miR-222-3p’s binding with CDKN1B. This release of CDKN1B mRNA leads to elevated CDKN1B protein expression, resulting in hypertrophy. In addition, we demonstrated that STAT3 which is activated by HG induces the transcription of NEAT1 by binding to its promoter. Our findings underscore an unexpected role of lncRNAs on gene regulation and introduce a new mode of proliferation regulation in mesangial cells.

Details

Language :
English
ISSN :
2296889X
Volume :
7
Database :
Directory of Open Access Journals
Journal :
Frontiers in Molecular Biosciences
Publication Type :
Academic Journal
Accession number :
edsdoj.0cba0ec7ce2a4bbaa01a7dc910428464
Document Type :
article
Full Text :
https://doi.org/10.3389/fmolb.2020.627827