Gao Haixia, Wang Mengbo, Xiong Shuchen, Zhang Ran, Wang Cancan, Zhang Huan, Ji Wenli, Wang Cuicui, Jia Zhiying, Li Xinxia
Departments of Pathology, The Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang, China.
Departments of Ultrasound, The Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang, China.
J Transl Med. 2025 Jul 22;23(1):807. doi: 10.1186/s12967-025-06689-8.
Both miR-193a-3p and T-Cell Leukemia/Lymphoma 1 (TCL1) are enriched in the PI3K/AKT signaling pathway, which is pivotal for the regulation of the initiation and progression of diffuse large B-cell lymphoma (DLBCL). Although miR-193a-3p has been demonstrated to exert an inhibitory effect in various tumors, the relationship between miR-193a-3p and TCL1, as well as the mechanisms by which miR-193a-3p participates in the modulation of DLBCL onset and progression, remain to be elucidated. The expression levels of miR-193a-3p and TCL1 in DLBCL cells were examined using quantitative real-time polymerase chain reaction (qRT-PCR), and their impact on DLBCL cell growth was assessed through cell proliferation assays and flow cytometry. Subsequently, the interaction between miR-193a-3p and TCL1 was investigated using a dual-luciferase reporter assay. A nude mouse model of subcutaneous DLBCL was established in which the mice were injected with miR-193a-3p agomir, and were evaluated after 45 days. Finally, the mechanism by which miR-193a-3p modulates the PI3K/AKT signaling pathway was explored via qRT-PCR and Western blotting analyses. It was found that miR-193a-3p is downregulated, while TCL1 is upregulated in DLBCL. miR-193a-3p was shown to inhibit proliferation and induce apoptosis in DLBCL cells, in contrast to TCL1, which promotes proliferation and suppresses apoptosis. Moreover, TCL1 was identified as a target gene of miR-193a-3p. Additionally, it was demonstrated that miR-193a-3p regulates the PI3K/AKT signaling pathway through TCL1 both in vitro and in vivo. Collectively, these findings indicate that miR-193a-3p suppresses the growth of DLBCL by targeting TCL1 within the PI3K/AKT signaling pathway.
The online version contains supplementary material available at 10.1186/s12967-025-06689-8.
miR-193a-3p和T细胞白血病/淋巴瘤1（TCL1）均在PI3K/AKT信号通路中富集，该信号通路对弥漫性大B细胞淋巴瘤（DLBCL）的起始和进展调节至关重要。尽管miR-193a-3p已被证明在各种肿瘤中发挥抑制作用，但miR-193a-3p与TCL1之间的关系，以及miR-193a-3p参与调节DLBCL发病和进展的机制仍有待阐明。使用定量实时聚合酶链反应（qRT-PCR）检测DLBCL细胞中miR-193a-3p和TCL1的表达水平，并通过细胞增殖试验和流式细胞术评估它们对DLBCL细胞生长的影响。随后，使用双荧光素酶报告基因检测法研究miR-193a-3p与TCL1之间的相互作用。建立皮下DLBCL裸鼠模型，给小鼠注射miR-193a-3p激动剂，45天后进行评估。最后，通过qRT-PCR和蛋白质免疫印迹分析探索miR-193a-3p调节PI3K/AKT信号通路的机制。研究发现，在DLBCL中miR-193a-3p表达下调，而TCL1表达上调。与促进增殖和抑制凋亡的TCL1相反，miR-193a-3p被证明可抑制DLBCL细胞的增殖并诱导其凋亡。此外，TCL1被确定为miR-193a-3p的靶基因。此外，还证明miR-193a-3p在体外和体内均通过TCL1调节PI3K/AKT信号通路。总的来说，这些发现表明miR-193a-3p通过靶向PI3K/AKT信号通路中的TCL1抑制DLBCL的生长。
在线版本包含可在10.1186/s12967-025-06689-8获取的补充材料。
