The Effect of miR-338-3p on Malignant Progression of Colorectal Cancer Cells through GPX4/ASCL4/ACSL3 Pathway

This study aims to investigate the effect of miR-338-3p on the malignant progression of CRC (colorectal cancer) cells by adjusting GPX4 (glutathione peroxidase 4)/ACSL4 (long chain acyl CoA synthase 4)/ACSL3 (long chain acyl CoA synthase 3) pathway. Human LS513 CRC cells were selected as the study subjects and randomly assigned into Control group, miR-NC group, miR-338-3p mimics group, miR-338-3p mimics+pcDNA-NC group, and miR-338-3p mimics+pcDNA-GPX4 group. qRT-PCR was used to detect the expression of miR-338-3p and GPX4 mRNA in cells. CCK8 and clone formation experiments were used to detect cell proliferation. Scratch experiment was used to detect cell migration. Transwell experiment was used to detect cell invasion. Western blot was used to detect the protein expression of GPX4, ACSL4, ACSL3, MMP-9, and Bcl-2 in cells. Dual luciferase assay was used to detect the targeting relationship between miR-338-3p and GPX4. For the Control group and miR-NC group, the miR-338-3p mimics group showed an increase in miR-338-3p, apoptosis rate, and ACSL4 and ACSL3 protein levels (P<0.05), and a decrease in GPX4 mRNA, survival rate, clone number, migration number, invasion number, and GPX4, MMP-9, and Bcl-2 protein levels (P<0.05). For the miR-338-3p mimics group and the miR-338-3p mimics+pcDNA-NC group, the miR-338-3p mimics+pcDNA-GPX4 group showed an increase in GPX4 mRNA, survival rate, clone number, migration number, invasion number, and GPX4, MMP-9, and Bcl-2 protein levels (P<0.05), and a decrease in apoptosis rate, and ACSL4 and ACSL3 protein levels (P<0.05). For the miR-NC+GPX4-WT group, the miR-338-3p mimics+GPX4-WT group showed a prominent decrease in dual luciferase activity (P<0.05). miR-338-3p may inhibit the malignant progres sion of CRC cells by adjusting GPX4/ASCL4/ACSL3 pathway.

CSTR: 32200.14.cjcb.2025.11.0012