Qin Xiaorong, Li Hongyan, Wu Jianqiu, Tang Weiyan, Li Wenjuan, Li Kejin
Department of Internal Medicine, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, People's Republic of China.
J Inflamm Res. 2024 Jul 1;17:4187-4197. doi: 10.2147/JIR.S453245. eCollection 2024.
Diffuse large B-cell lymphoma (DLBCL) is a prevalent malignant condition with a dismal prognosis. LncRNA PGM5 antisense RNA 1 (PGM5-AS1) appears to be intricately involved in the progression of DLBCL, yet the modulatory mechanism remains unclear. The purpose of this study was to explore the expression of lncRNA PGM5-AS1 in DLBCL and its effect on the disease progression of DLBCL, as well as to explore its mechanisms.
A total of 35 patients were included in the study. The expression levels of PGM5-AS1 and miR-503-5p in DLBCL tumor tissues and cell lines were detected by RT-qPCR. Cell proliferation was assessed using CCK8. Apoptosis rate was determined by flow cytometry. Cell invasion was examined by transwell assays. The specific interaction between PGM5-AS1 and miR-503-5p was verified through dual luciferase reporter gene assays. The immune related factors were detected by ELASA kits. The CD8 T cells cytotoxicity was evaluated by LDH cytotoxicity kit.
In DLBCL tumor tissues and cells, upregulated PGM5-AS1 expression, downregulated miR-503-5p expression, and elevated PD-L1 expression were observed. PGM5-AS1 functioned as a regulator in controlling DLBCL cell proliferation, apoptosis, and invasion by downregulating miR-503-5p expression. When CD8 T cells were co-cultured with cells transfected with si-PGM5-AS1, the secretion of immunoregulatory factors increased, and the cytotoxicity of CD8 T cells increased. These effects were mitigated by miR-503-5p inhibitors.
PGM5-AS1 accelerated DLBCL development and facilitated tumor immune escape through the miR-503-5p. Our discoveries offered an insight into lncRNA PGM5-AS1 serving as a prospective therapeutic target for DLBCL.
弥漫性大B细胞淋巴瘤（DLBCL）是一种常见的恶性疾病，预后较差。长链非编码RNA PGM5反义RNA 1（PGM5-AS1）似乎与DLBCL的进展密切相关，但其调节机制仍不清楚。本研究的目的是探讨长链非编码RNA PGM5-AS1在DLBCL中的表达及其对DLBCL疾病进展的影响，并探讨其机制。
本研究共纳入35例患者。采用RT-qPCR检测DLBCL肿瘤组织和细胞系中PGM5-AS1和miR-503-5p的表达水平。使用CCK8评估细胞增殖。通过流式细胞术测定凋亡率。通过Transwell实验检测细胞侵袭。通过双荧光素酶报告基因实验验证PGM5-AS1与miR-503-5p之间的特异性相互作用。使用ELISA试剂盒检测免疫相关因子。通过LDH细胞毒性试剂盒评估CD8 T细胞的细胞毒性。
在DLBCL肿瘤组织和细胞中，观察到PGM5-AS1表达上调、miR-503-5p表达下调和PD-L1表达升高。PGM5-AS1通过下调miR-503-5p表达，在控制DLBCL细胞增殖、凋亡和侵袭中发挥调节作用。当CD8 T细胞与转染了si-PGM5-AS1的细胞共培养时，免疫调节因子的分泌增加，CD8 T细胞的细胞毒性增加。miR-503-5p抑制剂可减轻这些作用。
PGM5-AS1通过miR-503-5p加速DLBCL的发展并促进肿瘤免疫逃逸。我们的发现为长链非编码RNA PGM5-AS1作为DLBCL的潜在治疗靶点提供了见解。
