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. 2024 Mar 1;16(5):4169-4190.
doi: 10.18632/aging.205565. Epub 2024 Mar 1.

RAB22A as a predictor of exosome secretion in the progression and relapse of multiple myeloma

Bingjie Fan  1   2 , Li Wang  1   2 , Jishi Wang  1   2
Affiliations

RAB22A as a predictor of exosome secretion in the progression and relapse of multiple myeloma

Bingjie Fan et al. Aging (Albany NY). .

Abstract

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.

Keywords: EMT; RAB22A; exosome secretion; immune regulation; multiple myeloma.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Differential analysis of expression level of RAB22A. (A) Differential expression analysis of RAB22A in normal people, MGUS, SMM and MM patients. (B) Differential expression of RAB22A in MSC of newly diagnosed and relapsed MM patients.
Figure 2
Figure 2
Differentially expressed genes and enrichment analysis in different RAB22A groups. (A, B) The differentially expressed genes of high and low RAB22A groups were presented by heatmap and volcano plot. (C, D) GO enrichment analysis was performed on differentially expressed genes.
Figure 3
Figure 3
Correlation analysis between RAB22A and EMT. (A, B) EMT-related genes with significantly different expression levels between high and low RAB22A groups. (C) EMT scores of high and low RAB22A groups were calculated. (D–R) Scatterplots and correlation of RAB22A and EMT-related genes.
Figure 4
Figure 4
Relationship between MM disease state and exosomes secretion. (A) Exosome scores of MSCs in newly diagnosed and recurrent patients. (B, C) Heatmap and boxplot showed the expression level of exosome-related genes in MSCs of newly diagnosed and relapsed MM patients.
Figure 5
Figure 5
Relationship between RAB22A and exosomes secretion. (A) Exosome scores in high and low RAB22A groups. (B, C) Expression level of exosome-related genes in high and low RAB22A groups. (D–N) Correlation and scatterplots between RAB22A and exosome-related genes.
Figure 6
Figure 6
Relationship between RAB22A and immune cell infiltration. (A, B) Infiltration level of immune cells in high and low RAB22A groups. (C) Correlation between RAB22A and infiltration level of immune cells. (D–J) Scatterplots of RAB22A and immune cell infiltration.
Figure 7
Figure 7
Relationship between RAB22A and immune checkpoint genes. (A) Heatmap showed the gene expression level of immune checkpoint genes in high and low RAB22A groups. (B) Boxplot showed the gene expression level of immune checkpoint genes in high and low RAB22A groups.
Figure 8
Figure 8
Relationship between RAB22A and m6A methylation. (A, B) Expression level of m6A methylation-related genes in different RAB22A groups. (C–G) Correlation and scatterplots between RAB22A and m6A methylation-related genes. (H, I) Nomogram and calibration curve of the risk of expressing RAB22A.
Figure 9
Figure 9
(A–C) Drugs with significantly different IC50 values between high and low RAB22A groups.
Figure 10
Figure 10
To verify the expression level of RAB22A in clinical samples and cell lines. (A–D) Western blotting results showed that the expression level of RAB22A protein in MM patients was significantly higher than that in normal people. (E, F) qRT-PCR results showed that the expression level of RAB22 gene in MM patients was significantly higher than that in normal people. (G) CCK-8 assay showed that the OD value decreased after down-regulating the expression of RAB22A in MM cell lines.
Figure 11
Figure 11
Effects of regulating RAB22A on exosomes secretion and cell proliferation. (A) Verification of exosomes by western blotting. (B) The exosomes of MSCs in control group and down-regulated RAB22A group were co-cultured with MM cell line, and the OD values of MM cells at different time points were detected by CCK-8 method. (C) The exosomes of control group and down-regulated RAB22A group were collected and stained with PKH26. The stained exosomes were co-cultured with MM cells, and the endocytosis of exosomes was observed under fluorescence microscope.
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References

    1. Palumbo A, Anderson K. Multiple myeloma. N Engl J Med. 2011; 364:1046–60. 10.1056/NEJMra1011442 - DOI - PubMed
    1. Weiss BM, Abadie J, Verma P, Howard RS, Kuehl WM. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood. 2009; 113:5418–22. 10.1182/blood-2008-12-195008 - DOI - PMC - PubMed
    1. Landgren O, Kyle RA, Pfeiffer RM, Katzmann JA, Caporaso NE, Hayes RB, Dispenzieri A, Kumar S, Clark RJ, Baris D, Hoover R, Rajkumar SV. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood. 2009; 113:5412–7. 10.1182/blood-2008-12-194241 - DOI - PMC - PubMed
    1. Rajkumar SV. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022; 97:1086–107. 10.1002/ajh.26590 - DOI - PMC - PubMed
    1. Zhao JH, Xu QL, Ma S, Li CY, Zhang HC, Zhao LJ, Zhang ZY. Recent advance of small-molecule drugs for clinical treatment of multiple myeloma. Eur J Med Chem. 2023; 257:115492. 10.1016/j.ejmech.2023.115492 - DOI - PubMed

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