MicroRNA-196a increases apoptosis in B cells through downregulation of FOXO1

Abstract

MicroRNAs (miRNAs) are key regulators of cancer pathogenesis, and their expression is often dysregulated in cancer cells. The role of miR-196a-5p has been investigated in various types of cancers. However, it is relatively less understood in B-cell malignancies. This study aimed to investigate the role of miR-196a-5p in B cells by using a human diffuse large B-cell lymphoma cell line, SU-DHL-6, and mouse B lymphocytes. The enforced expression of miR-196a in SU-DHL-6 cells increased daunorubicin-mediated apoptosis. Luciferase assay revealed that FOXO1 was a direct target of miR-196a-5p in SU-DHL-6 cells. The mRNA and protein expression of FOXO1 was downregulated in miR-196a-overexpressing SU-DHL-6 cells. In addition, miR-196a-5p was highly expressed in mouse bone marrow cells, compared with that of splenic B cells, and FOXO1 expression was negatively correlated with miR-196a-5p level. miR-196a-5p was upregulated by B-cell receptor stimulation, which was inversely correlated with FOXO1 expression in splenic B cells. Apoptosis was increased when miR-196a-5p was upregulated in murine primary B cells. These results identify miR-196a-5p as a post-transcriptional regulator of FOXO1 and indicate its importance in regulating B-cell malignancies and activation. © 2025 Elsevier B.V., All rights reserved.