The Role of miR-124-3p/UHRF1 in NaAsO2-Induced Apoptosis of LX-2 Cells via DNMT1/SOCS1

The exact molecular mechanism underlying arsenic-induced liver injury remains elusive. In this study, we investigated the role of NaAsO₂ in promoting Apoptosis in LX-2 cells via miR-124-3p/UHRF1 regulation of the DNMT1/SOCS1 axis. LX-2 cells were treated with different concentrations of NaAsO₂, miR-124-3p mimic, UHRF1 inhibitor NSC232003, and UHRF1 agonist. Cell viability, Apoptosis, and the expression of related proteins and mRNA were assessed using CCK-8, immunofluorescence, flow cytometry, Western blot, and RT-qPCR. Compared with the control group, NaAsO₂ significantly reduced cell activity, increased the levels of pro-apoptotic proteins Bax and Caspase3, and decreased the expression of anti-apoptotic protein BCL2. Flow cytometry analysis confirmed a significant increase in the Apoptosis rate. Following NaAsO₂ exposure, miR-124-3p expression was downregulated, while the mRNA and protein levels of UHRF1 and DNMT1 were upregulated, accompanied by reduced SOCS1 expression. Notably, co-treatment with either the miR-124-3p mimic or the UHRF1 inhibitor NSC232003 and NaAsO₂ significantly attenuated Apoptosis, downregulated UHRF1 and DNMT1 expression, and restored SOCS1 levels compared with NaAsO₂ treatment alone. In summary, NaAsO₂ induces Apoptosis in LX-2 cells by modulating the DNMT1/SOCS1 pathway through miR-124-3p/UHRF1 signaling. This study investigated the mechanism by which NaAsO₂ induces Apoptosis in LX-2 cells through the regulation of miR-124-3p/UHRF1 and DNMT1/SOCS1. The experiments revealed that NaAsO₂ decreased cell viability, upregulated pro-apoptotic proteins Bax and Caspase3, downregulated anti-apoptotic protein BCL2, and increased the Apoptosis rate. NaAsO₂ reduced the expression of miR-124-3p, increased the expression of UHRF1 and DNMT1, and inhibited SOCS1. The results indicated that miR-124-3p/UHRF1 regulation of DNMT1/SOCS1 played a role in NaAsO₂-induced Apoptosis of LX-2 cells.

DNMT1; NaAsO2; UHRF1; apoptosis; miR‐124‐3p.