Dataset Information

Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis.

ABSTRACT:

Background

Diabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2. Long non-coding RNAs (lncRNAs) are being found to be involved in the DN pathogenesis. In this study, we aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis.

Methods

The expression levels of PVT1, miR-23b-3p, and Wilms tumor protein 1 (WT1) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was performed to determine protein expression. Cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS) assay. The targeted correlation between miR-23b-3p and PVT1 or WT1 was verified by dual-luciferase reporter assay.

Results

PVT1 and WT1 were highly expressed in the serum of DN patients and high glucose (HG)-induced mesangial cells (MCs). The knockdown of PVT1 or WT1 ameliorated HG-induced proliferation and fibrosis in MCs. Mechanistically, PVT1 modulated WT1 expression through acting as a molecular sponge of miR-23b-3p. The miR-23b-3p/WT1 axis mediated the protective effect of PVT1 knockdown on HG-induced proliferation and fibrosis in MCs. The NF-?B pathway was involved in the regulatory network of the PVT1/miR-23b-3p/WT1 axis in HG-induced MCs.

Conclusion

Our study suggested that PVT1 knockdown ameliorated HG-induced proliferation and fibrosis in MCs at least partially by regulating the miR-23b-3p/WT1/NF-?B pathway. Targeting PVT1 might be a potential therapeutic strategy for DN treatment.

SUBMITTER: Zhong W

PROVIDER: S-EPMC7161221 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis.

Zhong Wen W Zeng Jiaoe J Xue Junli J Du Aimin A Xu Yancheng Y

Diabetology & metabolic syndrome 20200415

<h4>Background</h4>Diabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2. Long non-coding RNAs (lncRNAs) are being found to be involved in the DN pathogenesis. In this study, we aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis.<h4>Methods</h4>The expression levels of PVT1, miR-23b-3p, and Wilms tumor protein 1 (WT1) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-P ...[more]

PMID: 32322310

Similar Datasets

Project description:BackgroundTreating advanced colon cancer remains challenging in clinical settings because of the development of drug resistance and distant metastasis. Mechanisms underlying the metastasis of colon cancer are complex and unclear.MethodsComputational analysis was performed to determine genes associated with the exosomal long noncoding (lncRNA) plasmacytoma variant translocation 1 (PVT1)/vascular endothelial growth factor A (VEGFA) axis in patients with colon cancer. The biological importance of the exosomal lncRNA PVT1/VEGFA axis was examined in vitro by using HCT116 and LoVo cell lines and in vivo by using a patient-derived xenograft (PDX) mouse model through knockdown (by silencing of PVT1) and overexpression (by adding serum exosomes isolated from patients with distant metastasis (M-exo)).ResultsThe in silico analysis demonstrated that PVT1 overexpression was associated with poor prognosis and increased expression of metastatic markers such as VEGFA and epidermal growth factor receptor (EGFR). This finding was further validated in a small cohort of patients with colon cancer in whom increased PVT1 expression was correlated with colon cancer incidence, disease recurrence, and distant metastasis. M-exo were enriched with PVT1 and VEGFA, and both migratory and invasive abilities of colon cancer cell lines increased when they were cocultured with M-exo. The metastasis-promoting effect was accompanied by increased expression of Twist1, vimentin, and MMP2. M-exo promoted metastasis in PDX mice. In vitro silencing of PVT1 reduced colon tumorigenic properties including migratory, invasive, colony forming, and tumorsphere generation abilities. Further analysis revealed that PVT1, VEGFA, and EGFR interact with and are regulated by miR-152-3p. Increased miR-152-3p expression reduced tumorigenesis, where increased tumorigenesis was observed when miR-152-3p expression was downregulated.ConclusionExosomal PVT1 promotes colon cancer metastasis through its association with EGFR and VEGFA expression. miR-152-3p targets both PVT1 and VEGFA, and this regulatory pathway can be explored for drug development and as a prognostic biomarker.

Dataset Information

Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis.

Background

Methods

Results

Conclusion

Publications

Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets