Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, China.
PeerJ. 2023 Nov 6;11:e16388. doi: 10.7717/peerj.16388. eCollection 2023.
Diffuse large B-cell lymphoma (DLBCL) is a B-cell lymphoma with a high degree of aggressiveness. Recently, evidence has shown that miR-525-5p is decreased in DLBCL, suggesting its possible involvement in tumor progression. In this study, miR-525-5p suppressed proliferation, invasion and clonogenicity, and increased apoptosis of U2932 cells, whereas miR-525-5p silencing enhanced tumor cell growth. Next, miR-525-5p targets the 3'-UTR of Myd88, and Myd88 protein was increased in lymphoma tissues. Similar to the miR-525-5p mimic, Myd88 siRNA suppressed proliferation, invasion, and clonogenicity, and enhanced apoptosis of U2932 cells. We observed that Myd88 reversed the inhibitory effect of miR-525-5p on tumor cell growth by transfecting cells with miR-525-5p mimics alone or together with Myd88 overexpression vector. In addition, studies have shown that compared to the control group, U2932 cells with upregulated miR-525-5p expression have a reduced ability to induce tumor formation. In conclusion, our results demonstrate that miR-525-5p inhibits the progression of DLBCL through the Myd88/NF-κB pathway, which largely fills the gap of previous studies, and our results may provide a new reference for the targeted treatment of DLBCL.
弥漫性大 B 细胞淋巴瘤(DLBCL)是一种侵袭性较高的 B 细胞淋巴瘤。最近有证据表明,miR-525-5p 在 DLBCL 中表达降低,提示其可能参与肿瘤进展。在本研究中,miR-525-5p 抑制了 U2932 细胞的增殖、侵袭和克隆形成能力,同时增加了细胞凋亡,而 miR-525-5p 沉默则增强了肿瘤细胞的生长。接下来,miR-525-5p 靶向 Myd88 的 3'UTR,并且在淋巴瘤组织中 Myd88 蛋白增加。与 miR-525-5p 模拟物相似,Myd88 siRNA 抑制了 U2932 细胞的增殖、侵袭和克隆形成能力,同时增强了细胞凋亡。我们观察到,转染 miR-525-5p 模拟物单独或与 Myd88 过表达载体共转染细胞后,Myd88 逆转了 miR-525-5p 对肿瘤细胞生长的抑制作用。此外,研究表明,与对照组相比,上调 miR-525-5p 表达的 U2932 细胞诱导肿瘤形成的能力降低。总之,我们的研究结果表明,miR-525-5p 通过 Myd88/NF-κB 通路抑制 DLBCL 的进展,在很大程度上填补了以往研究的空白,我们的研究结果可能为 DLBCL 的靶向治疗提供新的参考。