LncRNA SNHG6 attenuates ferroptosis in high glucose-treated renal tubular epithelial cells by stabilizing YY1 to activate the PI3K/AKT/GSK-3β pathway
Brief intro:
- Author: Qiguo Wang, Qin Wang, Xiangyu Meng, Xiaoman Ji, Ting Wang
- Journal: Archives of Biochemistry and Biophysics
- Doi: https://www.doi.org/10.1016/j.abb.2025.110702
- Publication Date: 2025/12/11
Abstract
Ferroptosis has emerged as a critical mechanism contributing to renal tubular epithelial cell injury in diabetic nephropathy (DN), though its mechanisms require further elucidation. This study investigated the expression and regulatory role of long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) in DN-associated ferroptosis. Bioinformatics analysis confirmed the significant downregulation of SNHG6 in DN and its diagnostic value, while real-time quantitative PCR experiments demonstrated that high glucose treatment for 24 h induced the downregulation of SNHG6 in renal tubular epithelial cells HK-2. Overexpression of SNHG6 alleviated high glucose-triggered ferroptosis of HK-2 cells by promoting the expression of glutathione peroxidase 4 and reducing the expression of acyl-CoA synthetase long chain family member 4 and transferrin receptor, manifested by increased cell viability, decreased lactate dehydrogenase activity, and suppressed lipid peroxidation. Mechanistic studies revealed that SNHG6 stabilized YY1 mRNA by promoting its binding to the FUS RNA-binding protein, subsequently activating the PI3K/AKT/GSK-3β signaling pathway to exert a protective effect. Blocking the YY1-PI3K signaling cascade abolished SNHG6 overexpression-mediated inhibition of high glucose-induced cellular ferroptosis. In summary, SNHG6 exerts renoprotective effects in DN by modulating ferroptosis through the YY1-PI3K/AKT/GSK-3β axis.
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