Introduction and objective:
Long non-coding RNA XIST is implicated in various diseases, but its role in hearing loss remains unclear. The aim of the study is to investigate the function and molecular mechanism of XIST in oxidative stress-induced cochlear cell damage.

Material and methods:
XIST expression was quantified in clinical samples from presbycusis patients and normal controls. In vitro, the HEI-OC1 cochlear cell line was subjected to glucose oxidase (GO) treatment to mimic injury. XIST expression was knocked down using siRNA. Apoptosis was assessed by flow cytometry. Reactive oxygen species (ROS) levels were measured by DCFH-DA assay. Oxidative stress marker 4-HNE was evaluated. Dual-luciferase reporter assays and RNA pulldown analysis were employed to identify the interactions. Rescue experiments were conducted to elucidate the functional axis.

Results:
Elevated serum XIST levels in presbycusis patients were associated with a diagnostic AUC of 0.855. In HEI-OC1 cells, XIST knockdown under GO treatment markedly attenuated apoptosis, reduced ROS production, and decreased 4-HNE expression. XIST was confirmed to bind to and sequester miR-454-3p. PARP1 was identified as a direct target of miR-454-3p. MiR-454-3p inhibitor or PARP1 siRNA offset the protective effects of XIST knockdown against oxidative stress and apoptosis.

Conclusions:
LncRNA XIST can exacerbate oxidative stress-induced cochlear cell damage by sponging miR-454-3p and upregulating PARP1 expression.