Abstract

Exosomes, nanometer-sized membranous vesicles in body fluids, have emerged as promising non-invasive biomarkers for cancer diagnosis. However, the function of exosomes in diffuse large B-cell lymphoma (DLBCL) remains elusive. This study aimed to investigate the role of exosomal miR-107 in lymphomagenesis and explore its clinical significance. In this study, decreased exosomal miR-107, miR-375-3p, and upregulated exosomal miR-485-3p were detected in the plasma of DLBCL patients and showed potential diagnostic value. Downregulated miR-107 expression was associated with advanced Ann Arbor stage, high IPI score, LDH, and β2-MG level in DLBCL patients. Overexpression of miR-107 by miR-107 Agomir significantly abrogated cell proliferation, induced apoptosis, and inhibited cell invasion in vitro, and repressed tumor growth in vivo. Moreover, the downregulation of miR-107 went in the opposite direction. The target genes of miR-107 were mainly enriched in the PI3K-Akt, Hippo, and AMPK signaling pathways. Notably, upregulated 14-3-3η (YWHAH) was suppressed by miR-107 in DLBCL, suggesting that miR-107 may restrain tumorigenesis by targeting 14-3-3η. In summary, this study unveils the function of miR-107 in lymphomagenesis, highlighting its potential as a diagnostic and prognostic indicator and as a new therapeutic target in the management of DLBCL.

Highlights

  • Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma (NHL) and accounts for 30–40% of all newly diagnosed cases

  • In the Venn diagram, the overlap of the two datasets contains 14 Differentially expressed miRNAs (DEMs) (Figure 1B), and the expression patterns of the DEMs in the two Gene Expression Omnibus (GEO) datasets are shown in the heat map (Figure 1C)

  • The miRNA–mRNA interacting network based on the shared miRNAs was visualized using Cytoscape, which may reveal new interactions in the pathogenesis of diffuse large B-cell lymphoma (DLBCL)

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Summary

Introduction

Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma (NHL) and accounts for 30–40% of all newly diagnosed cases. 30–40% present relapsed or refractory to R-CHOP treatment within a year after diagnosis (Maurer et al, 2016). These groups of patients usually suffer an unfavorable outcome, with a 1-year overall survival (OS) of less than 20% (Vitolo et al, 2017). International prognostic index (IPI) score (based on age, tumor stage, LDH, performance status, and the number of extranodal disease sites), gene expression profiling, and immunohistochemical analysis are usually used to predict survival time. Given the heterogeneity of DLBCL, patients with identical IPI scores may exhibit striking heterogeneity in outcomes (Voltin et al, 2020). IPI shows limitations in estimating treatment efficacy. Accurate prognostic evaluation methods are needed to overcome the limitations of traditional methods

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