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

IF 6.5 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecules and Cells Pub Date : 2025-05-20 DOI:10.1016/j.mocell.2025.100223

Soyoung Kim , Mina Han , Hyun Ju Hwang , Young-Ho Ahn , Ho Joon Im , Sang-Hyun Hwang , Kyung-Nam Koh , Nayoung Kim

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引用次数: 0

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.

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MicroRNA-196a通过下调fox01增加B细胞凋亡。

MicroRNAs （miRNAs）是癌症发病的关键调控因子，其表达在癌细胞中经常失调。miR-196a-5p在各种类型的癌症中的作用已被研究，但在b细胞恶性肿瘤中的作用相对较少。本研究旨在通过人弥漫性大B细胞淋巴瘤（DLBCL）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。miR-196a在SU-DHL-6细胞中的强制表达增加了柔红霉素介导的细胞凋亡。荧光素酶检测显示FOXO1是SU-DHL-6细胞中miR-196a-5p的直接靶点。过表达mir -196a的SU-DHL-6细胞中FOXO1 mRNA和蛋白表达下调。此外，miR-196a-5p在小鼠骨髓（BM）细胞中高表达，与脾（SP） B细胞相比，FOXO1表达与miR-196a-5p水平呈负相关。miR-196a-5p在B细胞受体（BCR）刺激下上调，与SP B细胞中FOXO1的表达呈负相关。上调miR-196a-5p可增加小鼠原代B细胞的凋亡。这些结果确定了miR-196a-5p是fox01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。

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来源期刊

Molecules and Cells 生物-生化与分子生物学

CiteScore

6.60

自引率

10.50%

发文量

审稿时长

2.3 months

期刊介绍： Molecules and Cells is an international on-line open-access journal devoted to the advancement and dissemination of fundamental knowledge in molecular and cellular biology. It was launched in 1990 and ISO abbreviation is "Mol. Cells". Reports on a broad range of topics of general interest to molecular and cell biologists are published. It is published on the last day of each month by the Korean Society for Molecular and Cellular Biology.