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Exosome-transmitted circ_MMP2 promotes hepatocellular carcinoma metastasis by upregulating MMP2.
Molecular Oncology ( IF 6.6 ) Pub Date : 2020-05-06 , DOI: 10.1002/1878-0261.12637
Dengrui Liu 1 , Hongxia Kang 2 , Mingtai Gao 1 , Li Jin 3, 4 , Fang Zhang 4 , Dongqin Chen 5 , Mianli Li 6 , Linghui Xiao 7
Affiliation  

Exosomes released by tumor cells have been recently identified as important determinants of tumor progression. They often carry circular RNAs that are differentially expressed in tumors and may regulate tumorigenesis and metastasis. Here, we showed that supernatant of 97H hepatocellular carcinoma (HCC) cell line could promote metastasis in L02 human liver cells and HCC cell lines. Moreover, we determined that circ_MMP2 (has_circ_0039411) could be delivered by 97H- or LM3 cell-derived exosomes to L02 and HepG2 cell cultures. High expression of circ_MMP2 led to the upregulation of its host gene matrix metallopeptidase 2 (MMP2) via the sponging of miR-136-5p. Rescue assays demonstrated that miR-136-5p and MMP2 were two essential participants in HCC metastasis. Finally, high level of circ_MMP2 or MMP2, as well as low level of miR-136-5p, was correlated with low overall survival of HCC patients. Our study highlights a novel molecular pathway in HCC cell-derived exosomes.

中文翻译:

外泌体传递的circ_MMP2通过上调MMP2促进肝细胞癌转移。

肿瘤细胞释放的外泌体最近被确定为肿瘤进展的重要决定因素。它们通常携带在肿瘤中差异表达的环状 RNA,并可能调节肿瘤发生和转移。在这里,我们发现 97H 肝细胞癌 (HCC) 细胞系的上清液可以促进 L02 人肝细胞和 HCC 细胞系的转移。此外,我们确定 circ_MMP2 (has_circ_0039411) 可以通过 97H 或 LM3 细胞衍生的外泌体递送至 L02 和 HepG2 细胞培养物。circ_MMP2 的高表达导致其宿主基因基质金属肽酶 2 (MMP2) 通过 miR-136-5p 的海绵作用上调。救援分析表明,miR-136-5p 和 MMP2 是 HCC 转移的两个重要参与者。最后,高水平的 circ_MMP2 或 MMP2,以及低水平的 miR-136-5p,与 HCC 患者的低总生存率相关。我们的研究突出了 HCC 细胞衍生的外泌体中的一种新分子途径。
更新日期:2020-01-14
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