Palmitic acid reduces the methylation of the FOXO1 promoter to suppress the development of diffuse large B-cell lymphoma via modulating the miR-429/DNMT3A axis

Background : Patients with diffuse large B-cell lymphoma (DLBCL) experience high treatment resistance. Palmitic acid (PA) exhibits antitumor effects. This study aims to explore the molecular mechanisms of PA on DLBLC development. Methods : We detect miR-429, FOXO1, and DNMT3A in DLBCL tumors and cell lines without or with PA treatment. We evaluated cell viability, apoptosis, and autophagy-related proteins after PA treatment. The interactions among miR-429, DNMT3A, and FOXO1 were analyzed by the luciferase reporter assay and methylation-specific PCR (MSP). After transfecting the miR-429 inhibitor, NC inhibitor, sh-DNMT3A, sh-NC, oe-DNMT3A, or oe-NC, we detected the roles of miR-429 and DNMT3A in cell viability, cell mortality, and autophagy-related protein expressions in PA-treated DLBCL cell lines. The effects of PA were also investigated in DLBCL tumor-bearing mice models. Results : MiR-429 and FOXO1 were downregulated, and DNMT3A was upregulated in DLBCL related to the control group. We found that PA enhanced cell autophagy via upregulating miR-429 and downregulating DNMT3A. Luciferase reporter assay and MSP verified that miR-429 diminished FOXO1 methylation by directly inhibiting DNMT3A. Further experiments showed that PA promotes cell autophagy and suppresses DLBCL by upregulating miR-429 to regulate the DNMT3A/FOXO1 axis. Furthermore, PA decreased in vivo xenografted tumor development by regulating the miR-429/DNMT3A/FOXO1 axis. Conclusion : PA might regulate autophagy in DLBCL development via modulating the miR-429/DNMT3A/FOXO1 axis, which might be a new target to treat DLBCL.