Cancer-associated fibroblasts promote hepatocellular carcinoma progression through downregulation of exosomal miR-150-3p
Cancer-associated fibroblasts promote hepatocellular carcinoma progression through downregulation of exosomal miR-150-3p
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DOI：
10.1016/j.ejso.2020.08.002
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发表时间：
2021-01-29
期刊：
影响因子：
3.8
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Yugawa, Kyohei;Yoshizumi, Tomoharu;Mori, Masaki
目的：肝细胞癌（Hepatocellular carcinoma，HCC）是一种常见的恶性肿瘤. HCC的预后差，与肿瘤进展有关。HCC的恶性潜能受肿瘤微环境（TME）的调节。由于癌症相关成纤维细胞（CAF）有助于调节肿瘤进展，因此了解它们在HCC中的功能可以改善患者的预后。本研究的目的是确定来自CAFs的exosomes中的特异性microRNA（miRNAs）是否可能参与HCC的进展。方法：采用miRNA芯片技术分析HCC中来自CAFs和正常成纤维细胞（NF）的exosomes的miRNAs谱。进行迁移和侵袭测定以检查miR-150- 3 p在体外对HCC的作用。结果：miR-150 - 3 p在CAFs来源的exosomes中表达显著降低，并抑制HCC的迁移和侵袭。miR-150- 3 p通过exosomes从转染miR-150- 3 p的CAFs转移到HCC细胞，并消除HCC的迁移和侵袭。此外，HCC组织中miR-150- 3 p的低表达是HCC患者复发的重要风险因素。更重要的是，与血浆外泌体中miR-150 - 3 p水平较高的患者相比，血浆外泌体中miR-150 - 3 p水平较低的患者的生存率显著较差。结论：总体而言，我们的研究结果表明，CAFs来源的外泌体中抗肿瘤miR-150- 3 p的缺失极大地促进了HCC的进展。外泌体miR-150- 3 p是一种潜在的预后生物标志物，将载有miR-150- 3 p的外泌体转移到HCC细胞可能成为一种新的治疗选择。(C)2020年爱思唯尔有限公司，BASO类似于癌症外科协会和欧洲外科肿瘤学会。All rights reserved.
Purpose: Hepatocellular carcinoma (HCC) is a common and deadly cancer. The prognosis of HCC is poor and is related to tumor progression. The malignant potential of HCC is regulated by the tumor microenvironment (TME). As cancer-associated fibroblasts (CAFs) help regulate tumor progression, understanding how they function in HCC could improve patient outcomes. The aim of this study was to determine whether specific microRNAs (miRNAs) in exosomes derived from CAFs might be involved in HCC progression.Methods: MiRNA microarray assay was used to analyze miRNA profiles of exosomes derived from CAFs and normal fibroblasts (NFs) in HCC. Migration and invasion assays were performed to examine the effects of miR-150-3p on HCC in vitro. In addition, the relationships between prognosis of HCC patients and miR-150-3p expression in HCC tissues and plasma exosomes were retrospectively analyzed.Results: MiR-150-3p was significantly reduced in CAFs-derived exosomes, and inhibited HCC migration and invasiveness. MiR-150-3p was transferred from CAFs transfected miR-150-3p to HCC cells through exosomes, and abrogated HCC migration and invasiveness. Furthermore, low miR-150-3p expression in HCC tissues was a significant risk factor for recurrence in HCC patients. More importantly, survival rate in patients with low miR-150-3p levels in plasma exosomes was significantly poor compared with that in patients with high miR-150-3p levels.Conclusions: Overall, our findings suggest that the loss of antitumoral miR-150-3p in CAFs-derived exosomes greatly promotes HCC progression. Exosomal miR-150-3p is a potential prognostic biomarker, and transferring miR-150-3p-loaded exosomes to HCC cells might become a novel therapeutic option. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.