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

ABSTRACT The exact molecular mechanism underlying arsenic‐induced liver injury remains elusive. In this study, we investigated the role of NaAsO 2 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 NaAsO 2 , 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, NaAsO 2 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