Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1

Circular RNAs (circRNAs) are highly correlated with the progression and prognosis of hepatocellular carcinoma (HCC). In addition, mounting evidence has revealed that N6-methyladenosine (m6A) methylation, a common RNA modification, is involved in the progression of malignancies. In this research, a n...

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Autores principales:	Anqi Wu, Yuhao Hu, Yao Xu, Jing Xu, Xinyue Wang, Aiting Cai, Ruoyu Liu, Lin Chen, Feng Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	circular RNA HCC N6-methyladenosine hsa_circ_0058493 METTL3 YTHDC1 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bc43218f4a4e49b78133119c5fa78838
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spelling	oai:doaj.org-article:bc43218f4a4e49b78133119c5fa788382021-11-30T13:20:05ZMethyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 12296-634X10.3389/fcell.2021.762588https://doaj.org/article/bc43218f4a4e49b78133119c5fa788382021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.762588/fullhttps://doaj.org/toc/2296-634XCircular RNAs (circRNAs) are highly correlated with the progression and prognosis of hepatocellular carcinoma (HCC). In addition, mounting evidence has revealed that N6-methyladenosine (m6A) methylation, a common RNA modification, is involved in the progression of malignancies. In this research, a novel circRNA, hsa_circ_0058493, was proven to be upregulated in HCC, which was correlated with the prognosis of HCC patients. Experimentally, hsa_circ_0058493 knockdown suppressed the growth and metastasis of HCC cells in vivo and in vitro. On the contrary, the overexpression of hsa_circ_0058493 in HCC cells had the opposite effect in vitro. Mechanistic experiments revealed that hsa_circ_0058493 contained m6A methylation sites and that methyltransferase-like 3 (METTL3) mediated the degree of methylation modification of hsa_circ_0058493. Furthermore, YTH domain-containing protein 1 (YTHDC1) could bind to hsa_circ_0058493 and promote its intracellular localization from the nucleus to the cytoplasm. In addition, both si-METTL3 and si-YTHDC1 suppressed HCC cell growth and metastasis, whereas rescue experiments confirmed that overexpression of hsa_circ_0058493 inverted the inhibitory effects of si-METTL3 and si-YTHDC1 on HCC cells. Taken together, this study explored the oncogenic role of m6A-modified hsa_circ_0058493 and found to accelerate HCC progression via the METTL3-hsa_circ_0058493-YTHDC1 axis, indicating a potential therapeutic target for this deadly disease.Anqi WuYuhao HuYao XuJing XuXinyue WangAiting CaiRuoyu LiuLin ChenFeng WangFrontiers Media S.A.articlecircular RNAHCCN6-methyladenosinehsa_circ_0058493METTL3YTHDC1Biology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	circular RNA HCC N6-methyladenosine hsa_circ_0058493 METTL3 YTHDC1 Biology (General) QH301-705.5
spellingShingle	circular RNA HCC N6-methyladenosine hsa_circ_0058493 METTL3 YTHDC1 Biology (General) QH301-705.5 Anqi Wu Yuhao Hu Yao Xu Jing Xu Xinyue Wang Aiting Cai Ruoyu Liu Lin Chen Feng Wang Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1
description	Circular RNAs (circRNAs) are highly correlated with the progression and prognosis of hepatocellular carcinoma (HCC). In addition, mounting evidence has revealed that N6-methyladenosine (m6A) methylation, a common RNA modification, is involved in the progression of malignancies. In this research, a novel circRNA, hsa_circ_0058493, was proven to be upregulated in HCC, which was correlated with the prognosis of HCC patients. Experimentally, hsa_circ_0058493 knockdown suppressed the growth and metastasis of HCC cells in vivo and in vitro. On the contrary, the overexpression of hsa_circ_0058493 in HCC cells had the opposite effect in vitro. Mechanistic experiments revealed that hsa_circ_0058493 contained m6A methylation sites and that methyltransferase-like 3 (METTL3) mediated the degree of methylation modification of hsa_circ_0058493. Furthermore, YTH domain-containing protein 1 (YTHDC1) could bind to hsa_circ_0058493 and promote its intracellular localization from the nucleus to the cytoplasm. In addition, both si-METTL3 and si-YTHDC1 suppressed HCC cell growth and metastasis, whereas rescue experiments confirmed that overexpression of hsa_circ_0058493 inverted the inhibitory effects of si-METTL3 and si-YTHDC1 on HCC cells. Taken together, this study explored the oncogenic role of m6A-modified hsa_circ_0058493 and found to accelerate HCC progression via the METTL3-hsa_circ_0058493-YTHDC1 axis, indicating a potential therapeutic target for this deadly disease.
format	article
author	Anqi Wu Yuhao Hu Yao Xu Jing Xu Xinyue Wang Aiting Cai Ruoyu Liu Lin Chen Feng Wang
author_facet	Anqi Wu Yuhao Hu Yao Xu Jing Xu Xinyue Wang Aiting Cai Ruoyu Liu Lin Chen Feng Wang
author_sort	Anqi Wu
title	Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1
title_short	Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1
title_full	Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1
title_fullStr	Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1
title_full_unstemmed	Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1
title_sort	methyltransferase-like 3-mediated m6a methylation of hsa_circ_0058493 accelerates hepatocellular carcinoma progression by binding to yth domain-containing protein 1
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/bc43218f4a4e49b78133119c5fa78838
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Methyltransferase-Like 3-Mediated m6A Methylation of Hsa_circ_0058493 Accelerates Hepatocellular Carcinoma Progression by Binding to YTH Domain-Containing Protein 1

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