m6A结合蛋白LRPPRC促进多发性骨髓瘤的肿瘤发生

The m6A-Binding Protein LRPPRC Promotes the Tumorigenesis of Multiple Myeloma

摘要: 目的：探讨N6-甲基腺苷(N6-methyladenosine, m6A)结合蛋白富含亮氨酸的五肽重复蛋白(leucine-rich pentatricopeptide repeat-containing, LRPPRC)在多发性骨髓瘤(multiple myeloma, MM)中的临床意义及生物学功能。方法：采用生物信息学方法筛选MM中差异表达的m6A相关蛋白，qRT-PCR检测LRPPRC在MM患者骨髓样本中的表达水平，并通过qRT-PCR和western blot检测其在MM细胞系中的表达。通过体外实验CCK-8实验、细胞周期分析和凋亡实验评估LRPPRC对MM进展的影响。结果：多个数据库筛选出LRPPRC是MM中关键的差异表达m6A基因，其表达在MM患者中显著升高，并与MM分期及较差的预后密切相关。在U266、RPMI-8226和MM.1S三种MM细胞系及患者骨髓样本中证实LRPPRC高表达。此外，LRPPRC表达与ISS分期呈正相关。敲低LRPPRC可抑制MM细胞增殖，促进凋亡并诱导细胞周期阻滞。结论：本研究表明，LRPPRC可能成为MM潜在的预后标志物和治疗靶点。

Abstract: Objectives: To explore the clinical relevance and biological roles of the N6-methyladenosine (m6A) binding protein leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) in multiple myeloma (MM), aiming to offer new insights into its potential as a prognostic marker and therapeutic target for MM. Methods: Bioinformatics methodologies were employed to identify m6A-associated proteins exhibiting differential expression in MM. The expression levels of LRPPRC in the bone marrow of MM patients were assessed using Quantitative Real-Time PCR (qRT-PCR). Additionally, the expression of LRPPRC in MM cell lines was evaluated through qRT-PCR and Western blot analysis. In vitro experiments, including CCK-8 assays, cell cycle analyses, and apoptosis assays, were conducted to assess the impact of LRPPRC on MM progression. Results: We identified LRPPRC as a critical m6A differentially expressed gene in MM, observing that its expression was significantly upregulated in MM. This upregulation was positively correlated with the staging of MM and associated with poorer prognoses in MM patients. Furthermore, we confirmed elevated LRPPRC expression in three MM cell lines U266, RPMI-8226, and MM.1S as well as in the bone marrow of MM patients. Additionally, LRPPRC expression demonstrated a positive correlation with the International Staging System (ISS) stages of MM. Furthermore, LRPPRC knockdown inhibited the proliferation of MM cells, enhanced apoptosis, and induced cell cycle arrest. Conclusion: The study suggests that LRPPRC may serve as a potential prognostic target for MM.