LncRNA Small Nucleolar RNA Host Gene 11 Modulates Ferroptosis in Renal Tubular Epithelial Cells via miR-324-3p/GPX4 Axis in Acute Kidney Injury

Abstract

Role of ferroptosis in acute kidney injury (AKI) is not fully uncovered. We aim to explore a novel role that SNHG11/miR-324-3p modulated ferroptosis in AKI via modulating GPX4. To mimic AKI in vivo, 6-week male C57BL/6 mice were administrated with lipopolysaccharide (LPS). shRNA (sh-NC or sh-SNHG11), miRNA antagomir (antagomir-NC or miR-324-3p antagomir), miRNA agomir (agomir-NC and miR-324-3p agomir) were injected in mice to regulate SNHG11 and miR-324-3p, respectively. To stimulate the in vitro model of AKI, HK-2 cells were incubated with LPS for 6 h, followed by the transfection with shRNA (sh-NC or sh-SNHG11), miRNA mimics (mimics-NC or miR-324-3p mimics), miRNA inhibitor (inhibitor-NC and miR-324-3p inhibitor), respectively. Co-transfection of miR-324-3p mimics and SNHG11-wt decreased the relative luciferase activity, suggesting miR-324-3p was the target of SNHG11. SNHG11 silence increased miR-324-3p expression in LPS-stimulated HK-2 cells. Both of SNHG11 silence and miR-324-3p upregulation aggravated LPS-induced ferroptosis and kidney injury, and decreased GPX4 whereas downregulation of miR-324-3p inhibited LPS-caused impairment, and increased GPX4 in AKI models. In AKI models with SNHG11 silence, upregulation of miR-324-3p further enhanced ferroptosis and kidney injury, and resulted in the lower expression of GPX4. Decreased SNHG11 caused miR-324-3p upregulation in renal tubular epithelial cells, which led to GPX4 reduction that trigger ferroptosis in AKI.