Three isoforms of exosomal circPTGR1 promote hepatocellular carcinoma metastasis via the miR449a-MET pathway
Three isoforms of exosomal circPTGR1 promote hepatocellular carcinoma metastasis via the miR449a-MET pathway
复制标题
外泌体 circPTGR1 的三种亚型通过 miR449a-MET 途径促进肝细胞癌转移。
DOI：
10.1016/j.ebiom.2018.12.062
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发表时间：
2019-02-01
期刊：
影响因子：
11.1
通讯作者：
Chen, Guihua
中科院分区：
文献类型：
--
作者：
Wang, Guoying;Liu, Wei;Chen, Guihua
背景资料：方法：对非转移性（HepG2）、低转移性（97L）和高转移性（LM3）肝癌细胞的外泌体环状RNA（exosomal circular RNA，circRNA）进行序列测定。检测HCC患者血清中与转移相关的circRNA，并评估其与临床预后的关系。结果：LM3外泌体增强了HepG2和97 L细胞的细胞迁移和侵袭能力。CircPTGR 1是一种具有三种亚型的circRNA，在97 L和LM 3细胞的外泌体中特异性表达，在HCC患者的血清外泌体中上调，并与临床分期和预后相关。敲低circPTGR 1表达抑制了与LM 3外泌体共培养诱导的HepG2和97L细胞的迁移和侵袭。生物信息学、共表达分析和荧光素酶检测表明，circPTGR 1与MET竞争靶向miR449a.Interpretation：高转移性HCC细胞可以通过含有circPTGR 1的外泌体将这种潜力赋予那些低转移性或无转移性的细胞，从而增加这些细胞的迁移和侵袭能力。(C)2018由Elsevier B.V.出版
Background: The role of exosomal circular RNAs (circRNAs) in Hepatocellular carcinoma (HCC) cells with high metastatic potential has been little studied.Methods: Exosomal circRNA from cells with non-metastatic (HepG2), low metastatic (97L), and high metastatic (LM3) potential were sequencing. Metastatic-related circRNAs in serum from HCC patients were measured and their association with clinical prognosis was evaluated. Furthermore, candidate functional circRNAs in LM3-derived exosomes was assessed.Findings: LM3 exosomes enhanced the cell migration and invasion potential of HepG2 and 97 L cells. CircPTGR1, a circRNA with three isoforms, was specifically expressed in exosomes from 97 L and LM3 cells, upregulated in serum exosomes from HCC patients and was associated with the clinical stage and prognosis. Knockdown of circPTGR1 expression suppressed the migration and invasion of HepG2 and 97L cells induced by co-culturing with LM3 exosomes. Bioinformatics, co-expression analysis, and a luciferase assay indicated that circPTGR1 competed with MET to target miR449a.Interpretation: Higher metastatic HCC cells can confer this potential on those with lower or no metastatic potential via exosomes with circPTGR1, resulting in increased migratory and invasive abilities in those cells. (C) 2018 Published by Elsevier B.V.