LINC00942 Alleviates NaAsO2-induced Apoptosis by Promoting GSH Synthesis Through Targeting miR-214-5p

Abstract

The mechanism of arsenic-induced liver toxicity is not fully understood. This study aimed to investigate the role of LINC00942 in arsenic-induced hepatotoxicity by regulating miR-214-5p. As the exposure dose of NaAsO₂ gradually increases, cell viability, intracellular GSH content, ΔΨm, and the protein levels of GCLC and GCLM were reduced significantly. Apoptosis rate, ROS, and expression of apoptosis-related and NF-κB pathway proteins increased. The expression of LINC00942 was increased, while the expression of miR-214-5p was decreased. After suppressing LINC00942 levels, NaAsO₂ exposure further decreased cell viability, intracellular GSH content, ΔΨm, GCLC protein, and miR-214-5p expression. The apoptosis rate, ROS, and apoptosis-related and NF-κB pathway proteins further increased. miR-214-5p is targeted and negatively regulated by LINC00942. After miR-214-5p was overexpressed, NaAsO₂ further decreased cell viability, intracellular GSH content, ΔΨm, and GCLC protein expression compared to NaAsO₂ exposure. The apoptosis rate, ROS, apoptosis-related and NF-κB pathway proteins p65, and IKKβ were higher than those exposed to NaAsO₂. LINC00942 inhibitor along with miR-214-5p inhibitor combined with NaAsO₂ treatment resulted in increased cell viability, GSH, Bcl-2, and GCLC protein expression and decreased apoptosis rate, apoptosis related, p65, IKKβ protein, and ΔΨm, as compared to the combined NaAsO₂ and si LINC00942 group. NaAsO₂ exposure induces oxidative damage and apoptosis in LX-2 cells by activating NF-κB and inhibiting GSH synthesis. During this process, the expression level of LINC00942 increases, targeting to reduce the level of miR-214-5p, then weakening the effect of NaAsO₂ on NF-κB, thereby alleviating cellular oxidative damage and playing a protective role.

Keywords: Apoptosis; Arsenic; LINC00942; NF-κB; Oxidative damage; miR-214-5p.