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循环外泌体 miR-107 通过靶向 14-3-3η 抑制弥漫性大 B 细胞淋巴瘤的肿瘤发生。

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

作者信息

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

机构信息

Department of Hematology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

出版信息

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

DOI:10.3389/fcell.2021.667800
PMID:33987186
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8111223/
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 β-MG level in DLBCL patients. Overexpression of miR-107 by miR-107 Agomir significantly abrogated cell proliferation, induced apoptosis, and inhibited cell invasion , and repressed tumor growth . 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.

摘要

外泌体是体液中纳米级的膜性囊泡，已成为有前景的癌症诊断非侵入性生物标志物。然而，外泌体在弥漫性大B细胞淋巴瘤（DLBCL）中的功能仍不清楚。本研究旨在探讨外泌体miR-107在淋巴瘤发生中的作用，并探索其临床意义。在本研究中，检测到DLBCL患者血浆中外泌体miR-107、miR-375-3p降低，外泌体miR-485-3p上调，且显示出潜在的诊断价值。DLBCL患者中miR-107表达下调与Ann Arbor分期晚期、国际预后指数（IPI）评分高、乳酸脱氢酶（LDH）和β2-微球蛋白（β-MG）水平相关。通过miR-107激动剂过表达miR-107可显著抑制细胞增殖、诱导凋亡、抑制细胞侵袭并抑制肿瘤生长。此外，miR-107的下调则产生相反的作用。miR-107的靶基因主要富集于PI3K-Akt、Hippo和AMPK信号通路。值得注意的是，在DLBCL中miR-107可抑制上调的14-3-3η（YWHAH），提示miR-107可能通过靶向14-3-3η抑制肿瘤发生。总之，本研究揭示了miR-107在淋巴瘤发生中的功能，突出了其作为诊断和预后指标以及DLBCL治疗新靶点的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/34c50d47bda7/fcell-09-667800-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/da70cbda7fcb/fcell-09-667800-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/e9fd1bbaba5e/fcell-09-667800-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/29084c00d229/fcell-09-667800-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/de9f9efa94e6/fcell-09-667800-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/b73f8b17a874/fcell-09-667800-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/34c50d47bda7/fcell-09-667800-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/da70cbda7fcb/fcell-09-667800-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/e9fd1bbaba5e/fcell-09-667800-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/29084c00d229/fcell-09-667800-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/de9f9efa94e6/fcell-09-667800-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/b73f8b17a874/fcell-09-667800-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/844c/8111223/34c50d47bda7/fcell-09-667800-g006.jpg

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