Kim Soyoung, Han Mina, Hwang Hyun Ju, Ahn Young-Ho, Im Ho Joon, Hwang Sang-Hyun, Koh Kyung-Nam, Kim Nayoung
Asan Institute for Life Sciences and Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Mol Cells. 2025 Jul;48(7):100223. doi: 10.1016/j.mocell.2025.100223. Epub 2025 May 20.
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.
微小RNA（miRNA）是癌症发病机制的关键调节因子，其表达在癌细胞中常常失调。miR-196a-5p在多种癌症类型中的作用已得到研究。然而，在B细胞恶性肿瘤中对其了解相对较少。本研究旨在通过使用人弥漫性大B细胞淋巴瘤细胞系SU-DHL-6和小鼠B淋巴细胞来研究miR-196a-5p在B细胞中的作用。在SU-DHL-6细胞中强制表达miR-196a可增加柔红霉素介导的细胞凋亡。荧光素酶报告基因检测显示FOXO1是SU-DHL-6细胞中miR-196a-5p的直接靶标。在过表达miR-196a的SU-DHL-6细胞中，FOXO1的mRNA和蛋白表达下调。此外，与脾B细胞相比，miR-196a-5p在小鼠骨髓细胞中高表达，且FOXO1表达与miR-196a-5p水平呈负相关。B细胞受体刺激可上调miR-196a-5p，这与脾B细胞中FOXO1的表达呈负相关。当在小鼠原代B细胞中上调miR-196a-5p时，细胞凋亡增加。这些结果确定miR-196a-5p为FOXO1的转录后调节因子，并表明其在调节B细胞恶性肿瘤和激活中的重要性。
