miR-216a-5p promotes mesangial cell proliferation by targeting FoxO1 in diabetic nephropathy
Cong Huang1, Yi Zheng2, Yuanzhen Chen1
1Department of Nephrology, Shenzhen Guangming New District People's Hospital Shenzhen, China.
Background:
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide. microRNAs (miRNAs) have been reported to play essential roles in DN progression. However, the mechanism of miR-216a-5p on DN progression is still unclear.
Methods:
A DN model was established in human mesangial cells (HMC) by high glucose treatment. Cell proliferation was investigated using the cell counting kit-8 (CCK-8) assay. The cell cycle was measured through a propidium iodide (PI) cell cycle kit with flow cytometry. The interaction between miR-216a-5p and forkhead boxO1 (FoxO1) was probed by a bioinformatics analysis and luciferase activity assay. The expression of miR-216a-5p was detected using a quantitative real-time polymerase chain reaction (qRT-PCR). The abundances of FoxO1 and cell cycle-related cyclinD1, cyclin-dependent kinase 4 (CDK4), CDK6 and p27 were examined by qRT-PCR and Western blots (WB).
Results:
miR-216a-5p was up-regulated while FoxO1 was down-regulated in DN tissues. Moreover, miR-216a-5p promoted cell proliferation by regulating the cell cycle in high glucose-treated HMC cells. Notably, FoxO1 was a direct target and negatively correlated with miR-216a-5p. In addition, miR-216a induced cyclinD1, CDK4 and CDK6 but inhibited p27 expressions at the mRNA and protein levels. Furthermore, FoxO1 restoration reversed the regulatory effect of miR-216a on the cell cycle by regulating cyclinD1, CDK4, CDK6 and p27 abundances at the mRNA and protein levels.
Conclusion:
miR-216a-5p is ectopic in DN and it promotes cell proliferation through regulating the cell cycle by targeting FoxO1 in high glucose-stimulated HMC cells, indicating it may serve as a novel biomarker for DN treatment.
Insights
MicroRNA-216a-5p promotes diabetic nephropathy progression by affecting cell cycle regulation via targeting FoxO1. This microRNA may serve as a novel biomarker for diabetic nephropathy treatment.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Diabetic nephropathy (DN) is a major cause of end-stage renal disease.
- MicroRNAs (miRNAs) are implicated in DN pathogenesis, but miR-216a-5p's role remains unclear.
Purpose of the Study:
- To elucidate the mechanism of miR-216a-5p in diabetic nephropathy progression.
- To investigate the role of miR-216a-5p in regulating human mesangial cell (HMC) proliferation and cell cycle.
Main Methods:
- Established a DN model in HMCs using high glucose treatment.
- Assessed cell proliferation (CCK-8), cell cycle (flow cytometry), and gene/protein expression (qRT-PCR, WB).
- Investigated miR-216a-5p and FoxO1 interaction using bioinformatics and luciferase assays.
Main Results:
- miR-216a-5p was upregulated, and FoxO1 downregulated in DN tissues.
- miR-216a-5p promoted HMC proliferation by regulating the cell cycle, targeting FoxO1.
- miR-216a-5p modulated cell cycle proteins (cyclinD1, CDK4, CDK6, p27); FoxO1 restoration reversed these effects.
Conclusions:
- miR-216a-5p promotes DN progression by targeting FoxO1 and regulating the cell cycle in HMCs.
- miR-216a-5p may represent a novel therapeutic biomarker for diabetic nephropathy.
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