机构：[1]Department of Pediatric Surgery, the First Hospital of Lanzhou University, No.1 Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China[2]Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, 730000, Gansu, China[3]Department of Radiotherapy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Renmin South Rd 55#, Chengdu, 610041, Sichuan, China四川省人民医院四川省肿瘤医院[4]Laboratory for Advanced Interdisciplinary Research, the First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Lane, Wenzhou, 325000, Zhejiang, China[5]Department of Medical Oncology, Jiangsu Cancer Hospital＆The Affiliated Cancer Hospital of Nanjing Medical University, No.42 Baiziting Road, Xuanwu District, Nanjing, 210000, Jiangsu, China[6]Oncology Department, Binzhou Medical University Hospital, No.661 Huanghe 2nd Road, Binzhou, 256603, Shandong, China[7]Infectious Disease Department, Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu, 610072, Sichuan, China
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.
基金：
National Natural Science Foundation of
China (NO.81672928, 81571055, 81271225, 81171012) and Financial Grant from
the China Postdoctoral Science Foundation (NO.2017M621678).
第一作者机构：[1]Department of Pediatric Surgery, the First Hospital of Lanzhou University, No.1 Donggang West Road, Chengguan District, Lanzhou, 730000, Gansu, China
通讯作者：
通讯机构：[6]Oncology Department, Binzhou Medical University Hospital, No.661 Huanghe 2nd Road, Binzhou, 256603, Shandong, China[7]Infectious Disease Department, Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu, 610072, Sichuan, China[*1]Oncology Department, Binzhou Medical University Hospital, No.661 Huanghe 2nd Road, Binzhou, 256603, Shandong, China[*2]Infectious Disease Department, Hospital of Chengdu University of Traditional Chinese Medicine, No.39 Shi-er-qiao Road, Chengdu, 610072, Sichuan, China
推荐引用方式(GB/T 7714)：
Liu Dengrui,Kang Hongxia,Gao Mingtai,et al.Exosome-transmitted circ_MMP2 promotes hepatocellular carcinoma metastasis by upregulating MMP2[J].MOLECULAR ONCOLOGY.2020,14(6):1365-1380.doi:10.1002/1878-0261.12637.
医学