Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η

Jiarui Liu; Yang Han; Shunfeng Hu; Yiqing Cai; Juan Yang; Shuai Ren; Yi Zhao; Tiange Lu; Xiangxiang Zhou; Xin Wang

doi:10.3389/fcell.2021.667800

Circulating Exosomal MiR-107 Restrains Tumorigenesis in Diffuse Large B-Cell Lymphoma by Targeting 14-3-3η

Front Cell Dev Biol. 2021 Apr 27:9:667800. doi: 10.3389/fcell.2021.667800. eCollection 2021.

Authors

Jiarui Liu^{1

2}, Yang Han^{1

2}, Shunfeng Hu^{1

2}, Yiqing Cai^{1

2}, Juan Yang^{1

2}, Shuai Ren^{1

2}, Yi Zhao^{1

2}, Tiange Lu^{1

2}, Xiangxiang Zhou^{1

2

3

4

5

6}, Xin Wang^{1

2

3

4

5

6}

Affiliations

¹ Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
² Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.
³ School of Medicine, Shandong University, Jinan, China.
⁴ Shandong Provincial Engineering Research Center of Lymphoma, Jinan, China.
⁵ Branch of National Clinical Research Center for Hematologic Diseases, Jinan, China.
⁶ National Clinical Research Center for Hematologic Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China.

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.

Keywords: 14-3-3η; diffuse large B-cell lymphoma; exosome; miR-107; microRNAs.