CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis

Changshan Huang, Wei Yu, Qian Wang, Tao Huang, Yuechao Ding Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, People’s Republic of ChinaCorrespondence: Changshan HuangDepartment of Hepato-Biliary-Pancreatic Surgery, The...

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Autores principales: Huang C, Yu W, Wang Q, Huang T, Ding Y
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Publicado: Dove Medical Press 2021
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spelling oai:doaj.org-article:718c141da683482aa5950a622ca122f82021-11-09T18:40:35ZCircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis2253-5969https://doaj.org/article/718c141da683482aa5950a622ca122f82021-11-01T00:00:00Zhttps://www.dovepress.com/circantxr1-contributes-to-the-malignant-progression-of-hepatocellular--peer-reviewed-fulltext-article-JHChttps://doaj.org/toc/2253-5969Changshan Huang, Wei Yu, Qian Wang, Tao Huang, Yuechao Ding Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, People’s Republic of ChinaCorrespondence: Changshan HuangDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, People’s Republic of ChinaTel +86 371 65587028Email hnhcs@163.comBackground: Circular RNA (circRNA) is a key regulator for the malignant progression of cancer. However, the role of circRNA anthrax toxin receptor 1 (circANTXR1) in hepatocellular carcinoma (HCC) is still unclear.Methods: Quantitative real-time PCR was performed to detect RNA expression. Cell proliferation, migration and invasion were determined using MTT assay, EdU staining, colony formation assay, wound healing assay and transwell assay. The protein levels of metastasis markers, x-ray repair cross complementing 5 (XRCC5) and exosome markers were examined using Western blot analysis. Xenograft tumor models were built to investigate the role of circANTXR1 in HCC tumorigenesis. The relationship between microRNA (miR)-532-5p and circANTXR1 or XRCC5 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The identification of exosomes were performed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).Results: CircANTXR1 was a stable and highly expressed circRNA in HCC. Silenced circANTXR1 inhibited the proliferation, migration and invasion of HCC cells in vitro, and suppressed HCC tumor growth in vivo. MiR-532-5p could be sponged by circANTXR1, and its inhibitor could reverse the inhibition of circANTXR1 silencing on HCC cells progression. In addition, we discovered that XRCC5 was a target of miR-532-5p. Furthermore, XRCC5 overexpression could reverse the suppressive effect of miR-532-5p overexpression on HCC cell proliferation, migration and invasion. Exosome was involved in the transport of circANTXR1 in HCC cells. Exosome circANTXR1 might be a potential serum biomarker for HCC patients.Conclusion: CircANTXR1 promotes the progression of HCC through the miR-532-5p/XRCC5 axis, which might be a potential serum biomarker and therapeutic target of HCC.Keywords: hepatocellular carcinoma, circANTXR1, miR-532-5p, XRCC5, exosomeHuang CYu WWang QHuang TDing YDove Medical Pressarticlehepatocellular carcinomacircantxr1mir-532-5pxrcc5exosomeNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of Hepatocellular Carcinoma, Vol Volume 8, Pp 1339-1353 (2021)
institution DOAJ
collection DOAJ
language EN
topic hepatocellular carcinoma
circantxr1
mir-532-5p
xrcc5
exosome
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle hepatocellular carcinoma
circantxr1
mir-532-5p
xrcc5
exosome
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Huang C
Yu W
Wang Q
Huang T
Ding Y
CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis
description Changshan Huang, Wei Yu, Qian Wang, Tao Huang, Yuechao Ding Department of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, Henan, People’s Republic of ChinaCorrespondence: Changshan HuangDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450003, People’s Republic of ChinaTel +86 371 65587028Email hnhcs@163.comBackground: Circular RNA (circRNA) is a key regulator for the malignant progression of cancer. However, the role of circRNA anthrax toxin receptor 1 (circANTXR1) in hepatocellular carcinoma (HCC) is still unclear.Methods: Quantitative real-time PCR was performed to detect RNA expression. Cell proliferation, migration and invasion were determined using MTT assay, EdU staining, colony formation assay, wound healing assay and transwell assay. The protein levels of metastasis markers, x-ray repair cross complementing 5 (XRCC5) and exosome markers were examined using Western blot analysis. Xenograft tumor models were built to investigate the role of circANTXR1 in HCC tumorigenesis. The relationship between microRNA (miR)-532-5p and circANTXR1 or XRCC5 was confirmed by dual-luciferase reporter assay and RNA pull-down assay. The identification of exosomes were performed using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA).Results: CircANTXR1 was a stable and highly expressed circRNA in HCC. Silenced circANTXR1 inhibited the proliferation, migration and invasion of HCC cells in vitro, and suppressed HCC tumor growth in vivo. MiR-532-5p could be sponged by circANTXR1, and its inhibitor could reverse the inhibition of circANTXR1 silencing on HCC cells progression. In addition, we discovered that XRCC5 was a target of miR-532-5p. Furthermore, XRCC5 overexpression could reverse the suppressive effect of miR-532-5p overexpression on HCC cell proliferation, migration and invasion. Exosome was involved in the transport of circANTXR1 in HCC cells. Exosome circANTXR1 might be a potential serum biomarker for HCC patients.Conclusion: CircANTXR1 promotes the progression of HCC through the miR-532-5p/XRCC5 axis, which might be a potential serum biomarker and therapeutic target of HCC.Keywords: hepatocellular carcinoma, circANTXR1, miR-532-5p, XRCC5, exosome
format article
author Huang C
Yu W
Wang Q
Huang T
Ding Y
author_facet Huang C
Yu W
Wang Q
Huang T
Ding Y
author_sort Huang C
title CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis
title_short CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis
title_full CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis
title_fullStr CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis
title_full_unstemmed CircANTXR1 Contributes to the Malignant Progression of Hepatocellular Carcinoma by Promoting Proliferation and Metastasis
title_sort circantxr1 contributes to the malignant progression of hepatocellular carcinoma by promoting proliferation and metastasis
publisher Dove Medical Press
publishDate 2021
url https://doaj.org/article/718c141da683482aa5950a622ca122f8
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