Identification of miR-451 target genes as prognostic markers in diffuse large B-cell lymphoma

B-cell lymphoma, a diverse malignancy, is intricately regulated by multiple factors. MicroRNAs (miRNAs) have been demonstrated to be important regulators of the initiation and progression of human B-cell lymphoma, but their functions need to be further explored. Two B-cell lymphoma cell lines, Romas and HBL-1, were engineered to overexpress miR-451, with cell proliferation assessed via cell counting assays. Flow cytometry was used to study the effects of miR-451 on cell cycle and apoptosis. Bioinformatics analyses were performed using GEO datasets (GSE181063, GSE32918, GSE56315) to identify DEGs, and potential miR-451 target genes were predicted using tools like ENCORI, TargetScan, and R packages. A risk model for DLBCL prognosis was developed using Cox and LASSO regression. qRT-PCR validated the expression of these target genes. This study revealed that miR-451 inhibited cell proliferation, arrested the cell cycle, and induced apoptosis in human DLBCL cell lines. Bioinformatics analysis identified 9 target genes (<i>MMP9</i>, <i>AQP9</i>, <i>RIN2</i>, <i>EOMES</i>, <i>LCP2</i>, <i>SELPLG</i>, <i>MAL</i>, <i>SOCS5</i>, <i>S1PR3</i>) significantly associated with DLBCL prognosis, suggesting a potential mechanism by which miR-451 suppresses DLBCL development. Our study indicates that a specific set of miR-451 target genes may significantly influence DLBCL patient outcomes.

B细胞淋巴瘤（B-cell lymphoma）是一类异质性恶性肿瘤，受多种因素复杂调控。微RNA（microRNAs, miRNAs）已被证实是人类B细胞淋巴瘤发生与进展的重要调控因子，但其具体功能仍有待进一步探究。本研究构建了过表达miR-451的两种B细胞淋巴瘤细胞系Romas与HBL-1，并通过细胞计数实验评估细胞增殖情况；采用流式细胞术分析miR-451对细胞周期与细胞凋亡的影响。本研究利用GEO数据集（GSE181063、GSE32918、GSE56315）进行差异表达基因（differentially expressed genes, DEGs）筛选，并通过ENCORI、TargetScan及R语言包等工具预测miR-451的潜在靶基因；随后采用Cox回归与LASSO回归构建弥漫大B细胞淋巴瘤（diffuse large B-cell lymphoma, DLBCL）预后风险模型，并通过实时定量聚合酶链反应（quantitative real-time polymerase chain reaction, qRT-PCR）验证靶基因的表达水平。本研究发现，miR-451可抑制人类弥漫大B细胞淋巴瘤细胞系的细胞增殖、阻滞细胞周期并诱导细胞凋亡；生物信息学分析筛选出9个与DLBCL预后显著相关的靶基因，分别为MMP9、AQP9、RIN2、EOMES、LCP2、SELPLG、MAL、SOCS5、S1PR3，提示miR-451或通过调控上述靶基因抑制DLBCL的发生发展。本研究表明，一组特定的miR-451靶基因可显著影响DLBCL患者的预后结局。