研究概要
RAB22A是改善MM预后的潜在治疗靶点,其与外泌体分泌、EMT和免疫细胞浸润密切相关。
研究思路结论见上方概要
背景
多发性骨髓瘤(MM)是一种无法治愈的恶性浆细胞疾病。我们探索了RAB22A在外泌体分泌、上皮-间质转化(EMT)和免疫调节中的作用。
方法
我们从Gene Expression Omnibus (GEO)数据集中获取了MM样本。我们下载了“IOBR”包,并使用“PCA”和“ssGSEA”算法计算EMT评分和外泌体评分。使用“CIBERSORT”包分析免疫细胞的浸润。我们提取了间充质干细胞(MSC)的外泌体,以验证RAB22A的生物学功能。
结果
RAB22A在冒烟型多发性骨髓瘤(SMM)和MM患者中的表达水平显著高于正常人和意义未明的单克隆丙种球蛋白病(MGUS)患者,且复发MM患者中RAB22A的表达水平显著高于初诊患者。高RAB22A组的EMT评分和外泌体评分显著高于低RAB22A组,复发患者MSC的外泌体评分显著高于初诊患者。此外,单核细胞、静息NK细胞、嗜酸性粒细胞、调节性T细胞和活化CD4记忆T细胞的浸润水平与RAB22A呈正相关。下调MM-MSC中RAB22A的表达后,外泌体分泌减少。与si-RAB22A组MSC的外泌体相比,对照组外泌体显著促进MM的增殖。
展开英文摘要原文
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: RAB22A is a potential therapeutic target to improve the prognosis of MM, which is closely related to exosome secretion, EMT and immune cell infiltration.
论文信息
- 作者
- Fan B、Wang L、Wang J
- 单位
- 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.China
- 文献类型
- 非美国政府资助研究
- 期刊
- Aging2024 Mar 1