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LncRNA RAD51-AS1 Alleviates Oxidative Stress and Inflammation in Diabetic Nephropathy by Adsorbing miR-154-5p
Mengmeng Pu1, Yijun Chen2, Dewei Ouyang3
1Joint Orthopedics, Xingtai People's Hospital, Xingtai, China.
Introduction:
Diabetic nephropathy (DN) is one of the severe complications of diabetes. The specific roles and mechanisms of lncRNAs in DN remain to be further elucidated. This study aimed to investigate whether lncRNA RAD51-AS1 participates in oxidative stress and inflammatory responses in DN by regulating the miR-154-5p/MPC2 axis, and to elucidate its potential molecular mechanisms.
Methods:
This study included 74 patients with DN, 104 patients with type 2 diabetes alone, and 80 healthy controls, assessing their clinical indexes and gene expression. DN models were established using HK-2 cells treated with high-glucose (HG). Cell proliferation and apoptosis were assessed using CCK-8 assay and flow cytometry. Oxidative stress indicators and inflammatory factors were measured by ELISA. The targeting relationship was validated using dual-luciferase reporter assay.
Results:
Clinical studies indicated that serum RAD51-AS1 levels were downregulated in DN patients, and it was positively correlated with estimated glomerular filtration rate while negatively correlated with blood urea nitrogen, serum creatinine, and urinary albumin-to-creatinine ratio. Overexpression of RAD51-AS1 significantly inhibited HG-induced oxidative stress and inflammatory responses in HK-2 cells, manifested as enhanced cell proliferation, suppressed apoptosis, reduced levels of MDA, IL-6, IL-1β, and TNF-α, and increased SOD activity. Furthermore, overexpression of miR-154-5p reversed protective effect of RAD51-AS1 on cell injury. In addition, as an endogenous competitive RNA, RAD51-AS1 adsorbed miR-154-5p, thereby releasing its suppression of the target gene MPC2.
Conclusion:
RAD51-AS1 is downregulated in DN, and it regulates MPC2 by adsorbing miR-154-5p, thereby participating in oxidative stress and inflammatory responses in DN. This study elucidated a novel mechanism of RAD51-AS1/miR-154-5p/MPC2 axis in DN pathogenesis, providing potential theoretical basis and new targets for therapy of DN.
