Exosomal microRNA-25 released from cancer cells targets SIK1 to promote hepatocellular carcinoma tumorigenesis
Exosomal microRNA-25 released from cancer cells targets SIK1 to promote hepatocellular carcinoma tumorigenesis
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癌细胞释放的外泌体microRNA-25靶向SIK1促进肝细胞癌肿瘤发生
DOI：
10.1016/j.dld.2021.07.017
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发表时间：
2022-07-01
影响因子：
4.5
通讯作者：
Huang, Yan
中科院分区：
文献类型：
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作者：
Fu, Xiaoyu;Tang, Yujing;Huang, Yan
背景：肝细胞癌（HCC）被认为是全世界癌症相关死亡的主要原因。我们的研究旨在探讨HCC细胞系CSQT-2分泌的外泌体影响HCC进展的机制。方法：从CSQT-2细胞中提取外泌体。应用集落形成、Transwell、球体形成和流式细胞术分析来评估细胞生物活性。微阵列分析检测外泌体处理后 microRNA (miRNA) 表达的变化，然后进行 RT-qPCR 验证。应用荧光素酶报告基因检测SIK1与miR-25之间的结合。裸鼠异种移植研究显示了miR-25和SIK1的肿瘤生长和转移能力。结果：外泌体处理在体外增强了细胞恶性表型，在体内增强了肿瘤生长和肝肺转移。外泌体提高了 HCC 细胞中 miR-25 的表达。 miR-25 靶向 SIK1，SIK1 在外泌体处理的细胞中减少。 miR-25 抑制剂可降低细胞恶性表型并减弱体内肿瘤发生和转移。 SIK1 沉默可逆转 miR-25 抑制剂的作用。外泌体处理增强了细胞中的 Wnt/β-catenin 通路，而 miR-25 抑制剂则减弱了该通路的活性。 结论：miR-25 穿梭于 CSQT-2 衍生的外泌体中，通过减少 SIK1 表达并增强 Wnt/β-catenin 通路，促进 HCC 的发展。 (C) 2021 Editrice Gastroenterologica Italiana S.r.l.由爱思唯尔有限公司出版。保留所有权利。
Background: Hepatocellular carcinoma (HCC) is recognized as a leading cause of cancer-associated fatality worldwide. Our study here aimed to probe the mechanism by which exosomes secreted by CSQT-2, an HCC cell line, affected the progression of HCC.Methods: Exosomes were extracted from CSQT-2 cells. Colony formation, Transwell, sphere formation and flow cytometric analyses were applied to assess cell biological activities. Microarray analysis detected the change of microRNA (miRNA) expression after exosome treatment, followed by RT-qPCR validation. Luciferase reporter was applied to detect the binding between SIK1 and miR-25. Xenograft studies in nude mice manifested tumor growth and metastatic ability of miR-25 and SIK1.Results: The exosome treatment enhanced cell malignant phenotype in vitro and tumor growth and liver and lung metastases in vivo. The exosomes elevated miR-25 expression in HCC cells. miR-25 targeted SIK1 which was decreased in the exosomes-treated cells. miR-25 inhibitor reduced cell malignant phenotype and attenuated tumorigenesis and metastasis in vivo. SIK1 silencing reversed the effect of miR-25 inhibitor. The exosome treatment potentiated the Wnt/beta-catenin pathway in cells, whereas miR-25 inhibitor blunted the pathway activity.Conclusion: MiR-25 shuttled through CSQT-2-derived exosomes promoted the development of HCC by reducing SIK1 expression and potentiating the Wnt/beta-catenin pathway. (C) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.