Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guizhou Province Institute of Hematology, Guizhou Province Laboratory of Hematopoietic Stem Cell Transplantation Centre, Guiyang, China.
Clinical Medicine College of Guizhou Medical University, Guiyang, China.
Aging (Albany NY). 2024 Mar 1;16(5):4169-4190. doi: 10.18632/aging.205565.
Multiple myeloma (MM) is an incurable malignant plasma cell disease. We explored the role of RAB22A in exosome secretion, epithelial-mesenchymal transition (EMT) and immune regulation.
We obtained MM samples from Gene Expression Omnibus (GEO) data sets. We downloaded the "IOBR" package, and used the "PCA" and "ssGSEA" algorithms to calculate the EMT scores and exosome scores. The "CIBERSORT" package was used to analyze the infiltration of immune cells. We extracted the exosomes of mesenchymal stem cell (MSC) to verify the biological function of RAB22A.
The expression level of RAB22A in smoldering multiple myeloma (SMM) and MM patients was significantly higher than that in normal people and monoclonal gammopathy of undetermined significance (MGUS) patients, and the expression level of RAB22A in relapse MM patients was significantly higher than that in newly diagnosed patients. The EMT scores and exosome scores of high RAB22A group were significantly higher than those of low RAB22A group, and the exosome scores of MSC in recurrent patients were significantly higher than those of newly diagnosed patients. In addition, the infiltration levels of monocyte, NK cells resting, eosinophils, T cells regulatory and T cells CD4 memory activated were positively correlated with RAB22A. After down-regulating the expression of RAB22A in MM-MSC, the secretion of exosomes decreased. Compared with the exosomes of MSC in si-RAB22A group, the exosomes in control group significantly promoted the proliferation of MM.
RAB22A is a potential therapeutic target to improve the prognosis of MM, which is closely related to exosome secretion, EMT and immune cell infiltration.
多发性骨髓瘤（MM）是一种不可治愈的恶性浆细胞疾病。我们探索了 RAB22A 在细胞外囊泡分泌、上皮-间充质转化（EMT）和免疫调节中的作用。
我们从基因表达综合数据库（GEO）数据集获得 MM 样本。我们下载了“IOBR”软件包，并使用“PCA”和“ssGSEA”算法计算 EMT 评分和细胞外囊泡评分。使用“CIBERSORT”软件包分析免疫细胞浸润情况。我们提取间充质干细胞（MSC）的细胞外囊泡来验证 RAB22A 的生物学功能。
冒烟型多发性骨髓瘤（SMM）和 MM 患者中 RAB22A 的表达水平明显高于正常人及单克隆丙种球蛋白病不确定意义（MGUS）患者，复发 MM 患者的表达水平明显高于初诊患者。高 RAB22A 组的 EMT 评分和细胞外囊泡评分明显高于低 RAB22A 组，复发患者的 MSC 细胞外囊泡评分明显高于初诊患者。此外，单核细胞、NK 细胞静息、嗜酸性粒细胞、T 细胞调节和 T 细胞 CD4 记忆激活的浸润水平与 RAB22A 呈正相关。下调 MM-MSC 中 RAB22A 的表达后，细胞外囊泡的分泌减少。与 si-RAB22A 组 MSC 的细胞外囊泡相比，对照组的细胞外囊泡明显促进了 MM 的增殖。
RAB22A 是改善 MM 预后的潜在治疗靶点，与细胞外囊泡分泌、EMT 和免疫细胞浸润密切相关。
