Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma

Circular RNA (circRNA) can participate in various biological processes, including tumorigenesis, through their microRNA response elements. Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and their clinical significance remain unclear. Here, we present extensive anal...

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Main Authors: Liman Qiu, Yanbing Huang, Zhenli Li, Xiuqing Dong, Geng Chen, Haipo Xu, Yongyi Zeng, Zhixiong Cai, Xiaolong Liu, Jingfeng Liu
Format: Article
Language:English
Published: Wiley 2019-02-01
Series:Molecular Oncology
Subjects:
Online Access:https://doi.org/10.1002/1878-0261.12424
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author Liman Qiu
Yanbing Huang
Zhenli Li
Xiuqing Dong
Geng Chen
Haipo Xu
Yongyi Zeng
Zhixiong Cai
Xiaolong Liu
Jingfeng Liu
author_facet Liman Qiu
Yanbing Huang
Zhenli Li
Xiuqing Dong
Geng Chen
Haipo Xu
Yongyi Zeng
Zhixiong Cai
Xiaolong Liu
Jingfeng Liu
author_sort Liman Qiu
collection DOAJ
description Circular RNA (circRNA) can participate in various biological processes, including tumorigenesis, through their microRNA response elements. Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and their clinical significance remain unclear. Here, we present extensive analysis of circRNA profiles in tumor and matched peritumor tissues collected from 10 HCC patients, conducted to identify circRNA related to HCC progression. A total of 42 dysregulated circRNA (38 down‐regulated and 4 up‐regulated) were identified in HCC tumor tissues compared with matched peritumor tissues, revealing the heterogeneity of circRNA profiles in HCC. CircADAMTS13, derived from Exon 13–14 of the ADAMTS13 gene, was significantly downregulated in HCC tumor tissues. Furthermore, clinicopathological analysis revealed that up‐regulation of circADAMTS13 was negatively associated with tumor size but positively associated with prognosis. In addition, overexpression of circADAMTS13 could markedly inhibit HCC cell proliferation in vitro. Bioinformatic analysis and luciferase reporter assays further revealed that circADAMTS13 directly interacts with microRNA (miR)‐484. Rescue experiments showed that miR‐484 mimics can reverse the tumor‐suppressing roles of circADAMTS13 in HCC. Therefore, our results demonstrated that circADAMTS13 can serve as a tumor suppressor during HCC progression via the functional pathway of sponging miR‐484.
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spelling doaj.art-d86871785f4840ddb1db9f96f3ac955b2022-12-21T20:20:22ZengWileyMolecular Oncology1574-78911878-02612019-02-0113244145510.1002/1878-0261.12424Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinomaLiman Qiu0Yanbing Huang1Zhenli Li2Xiuqing Dong3Geng Chen4Haipo Xu5Yongyi Zeng6Zhixiong Cai7Xiaolong Liu8Jingfeng Liu9The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaThe United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province Mengchao Hepatobiliary Hospital of Fujian Medical University Fuzhou ChinaCircular RNA (circRNA) can participate in various biological processes, including tumorigenesis, through their microRNA response elements. Alterations in circRNA profiles during hepatocellular carcinoma (HCC) progression and their clinical significance remain unclear. Here, we present extensive analysis of circRNA profiles in tumor and matched peritumor tissues collected from 10 HCC patients, conducted to identify circRNA related to HCC progression. A total of 42 dysregulated circRNA (38 down‐regulated and 4 up‐regulated) were identified in HCC tumor tissues compared with matched peritumor tissues, revealing the heterogeneity of circRNA profiles in HCC. CircADAMTS13, derived from Exon 13–14 of the ADAMTS13 gene, was significantly downregulated in HCC tumor tissues. Furthermore, clinicopathological analysis revealed that up‐regulation of circADAMTS13 was negatively associated with tumor size but positively associated with prognosis. In addition, overexpression of circADAMTS13 could markedly inhibit HCC cell proliferation in vitro. Bioinformatic analysis and luciferase reporter assays further revealed that circADAMTS13 directly interacts with microRNA (miR)‐484. Rescue experiments showed that miR‐484 mimics can reverse the tumor‐suppressing roles of circADAMTS13 in HCC. Therefore, our results demonstrated that circADAMTS13 can serve as a tumor suppressor during HCC progression via the functional pathway of sponging miR‐484.https://doi.org/10.1002/1878-0261.12424cell proliferationcircular ADAMTS13circular RNAhepatocellular carcinomamicroRNA‐484
spellingShingle Liman Qiu
Yanbing Huang
Zhenli Li
Xiuqing Dong
Geng Chen
Haipo Xu
Yongyi Zeng
Zhixiong Cai
Xiaolong Liu
Jingfeng Liu
Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma
Molecular Oncology
cell proliferation
circular ADAMTS13
circular RNA
hepatocellular carcinoma
microRNA‐484
title Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma
title_full Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma
title_fullStr Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma
title_full_unstemmed Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma
title_short Circular RNA profiling identifies circADAMTS13 as a miR‐484 sponge which suppresses cell proliferation in hepatocellular carcinoma
title_sort circular rna profiling identifies circadamts13 as a mir 484 sponge which suppresses cell proliferation in hepatocellular carcinoma
topic cell proliferation
circular ADAMTS13
circular RNA
hepatocellular carcinoma
microRNA‐484
url https://doi.org/10.1002/1878-0261.12424
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