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Hsa_circ_0008360 promotes high glucose-induced damage in HK-2 cells via miR-346/WNT2B axis
1Endocrinology Department, Tangdu Hospital of Air Force Medical University, No. 1 Xinsi Road, Baqiao District, Xi'an, 710038, Shaanxi, China.
Background:
Diabetic nephropathy (DN) is a leading cause of end-stage renal disease worldwide. Recent researches have shown that circular RNAs (circRNAs) could affect the progress of DN, but the mechanism is still indistinct. In this work, we explored the roles of hsa_circ_0008360 in DN.
Methods:
The levels of hsa_circ_0008360, microRNA-346 (miR-346) and Winglesstype family member 2B (WNT2B) were indicated by quantitative real-time polymerase chain reaction (qRT-PCR) in DN tissues and HK2 cells. Meanwhile, the protein level of WNT2B was quantified by Western blot analysis. Besides, the function of cells was examined by Cell Counting Kit-8 (CCK8) assay, flow cytometry assay, western blot, and ELISA kit. Furthermore, the interplay between miR-346 and hsa_circ_0008360 or WNT2B was detected by dual-luciferase reporter assay.
Results:
The levels of hsa_circ_0008360 and WNT2B were increased, and the miR-346 level was decreased in the serum of DN patients and HG-treated HK2 cells. For functional analysis, hsa_circ_0008360 deficiency promoted cell viability, inhibits cell apoptosis, inflammatory response, and the synthesis of related fibrotic proteins in HG-treated HK2 cells. Moreover, overexpression of miR-346 induced the proliferation and inhibit apoptosis of HG-induced HK2 cells by inhibiting WNT2B expression. In mechanism, hsa_circ_0008360 acted as a miR-346 sponge to regulate the level of WNT2B.
Conclusion:
Hsa_circ_0008360 can regulate miR-346/WNT2B axis in HG-induced HK2 cells, providing an underlying targeted therapy for DN patients.
Insights
Circular RNAs (circRNAs) like hsa_circ_0008360 play a role in diabetic nephropathy (DN). This study shows hsa_circ_0008360 regulates the miR-346/WNT2B pathway, offering a potential therapeutic target for DN.
Area of Science:
- Molecular Biology
- Genetics
- Nephrology
Background:
- Diabetic nephropathy (DN) is a major cause of kidney failure.
- The precise mechanisms of DN progression involving circular RNAs (circRNAs) remain unclear.
- This study investigates the role of hsa_circ_0008360 in DN pathogenesis.
Purpose of the Study:
- To explore the function and mechanism of hsa_circ_0008360 in diabetic nephropathy.
- To elucidate the regulatory relationship between hsa_circ_0008360, microRNA-346 (miR-346), and Wingless-type family member 2B (WNT2B) in DN.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blot to measure molecule levels.
- Cell Counting Kit-8 (CCK8), flow cytometry, and ELISA for functional assays.
- Dual-luciferase reporter assay to confirm molecular interactions.
Main Results:
- hsa_circ_0008360 and WNT2B levels were elevated, while miR-346 was decreased in DN patients and high-glucose treated cells.
- hsa_circ_0008360 deficiency improved cell viability and reduced apoptosis and fibrosis.
- hsa_circ_0008360 functions as a miR-346 sponge, regulating WNT2B expression.
Conclusions:
- hsa_circ_0008360 modulates the miR-346/WNT2B axis in high-glucose-induced kidney cells.
- The hsa_circ_0008360/miR-346/WNT2B pathway presents a potential therapeutic target for diabetic nephropathy.
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