LINC01004/hsa-mir-125b-2-3p axis restrains ferroptosis in hepatocellular carcinoma by targeting HSPA4 via ceRNA mechanism

Background Hepatocellular carcinoma (HCC) is a primary cancer, accounting for 90% of primary liver cancer, mainly occurring in patients with cirrhosis and chronic liver disease. Objective To investigate the latent mechanisms of hepatocellular carcinoma (HCC) and find therapeutic targets. Methods Differentially expressed and overall survival related genes of HCC, and cell death related genes were intersected to obtain latent target genes. These genes were analyzed using ROC curve for diagnosing HCC. RT-qPCR and Western blot were performed to detect the expression level of genes. Wound healing tests were performed with or without si-HSPA4. Potential ceRNA axis was forecasted using TargetScan and miRanda and the dual luciferase reporter gene assay was used to verify the results. Finally, the images of H&E dye liquor-stained HCC tissue section, the CT images for patients in different tumor stage. Results LINC01004/hsa-miR-125b-2-3p/HSPA4 axis was forecasted and then was verified using dual-luciferase reporter assay. HSPA4 knockdown caused significant reduction of cell proliferation and ferroptosis. Si-HSPA4 related ferroptosis was generated through impairing iron transport via targeting restrain GPX4. For human subjects, the RT-qPCR analysis revealed the that the larger the tumor diameter, the higher the LINC01004, HSPA4, and GPX4 expression, and the lower the hsa-miR-125b-2-3p expression. Conclusion LINC01004/hsa-miR-125b-2-3p/HSPA4 regulatory axis involved in the ferroptosis of the progression of HCC via GPX4 dependent method, providing new therapeutic targets for HCC patients.