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LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation

The N6-methyladenosine (m6A) RNA methyltransferase METTL16 is an emerging player in RNA modification landscape and responsible for the deposition of m6A in a few transcripts. AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development including hepatocellular carcinoma (HCC). Nev...

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Autores principales: Wang, Yingchao, Zhong, Yue, Zheng, Xiaoyuan, Cheng, Niangmei, Yang, Yong, Yang, Ye, Wang, Fei, Zhuang, Qiuyu, Huang, Yao, Guo, Wuhua, Liao, Naishun, Yang, Xiaoyu, Zhao, Bixing, Liu, Xiaolong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541412/
https://www.ncbi.nlm.nih.gov/pubmed/37773181
http://dx.doi.org/10.1038/s41420-023-01620-w
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author Wang, Yingchao
Zhong, Yue
Zheng, Xiaoyuan
Cheng, Niangmei
Yang, Yong
Yang, Ye
Wang, Fei
Zhuang, Qiuyu
Huang, Yao
Guo, Wuhua
Liao, Naishun
Yang, Xiaoyu
Zhao, Bixing
Liu, Xiaolong
author_facet Wang, Yingchao
Zhong, Yue
Zheng, Xiaoyuan
Cheng, Niangmei
Yang, Yong
Yang, Ye
Wang, Fei
Zhuang, Qiuyu
Huang, Yao
Guo, Wuhua
Liao, Naishun
Yang, Xiaoyu
Zhao, Bixing
Liu, Xiaolong
author_sort Wang, Yingchao
collection PubMed
description The N6-methyladenosine (m6A) RNA methyltransferase METTL16 is an emerging player in RNA modification landscape and responsible for the deposition of m6A in a few transcripts. AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development including hepatocellular carcinoma (HCC). Nevertheless, it remains unclear whether METTL16 mediated m6A modification of lncRNAs can regulate AURKA activation in cancer progression. Here we aimed to investigate the functional links between lncRNAs and the m6A modification in AURKA signaling and HCC progression. Here we show that LncRNA TIALD (transcript that induced AURKA Lysosomal degradation) was down-regulated in HCC tissues by METTL16 mediated m6A methylation to facilitate its RNA degradation, and correlates with poor prognosis. Functional assays reveal that TIALD inhibits HCC metastasis both in vitro and in vivo. Mechanistically, TIALD directly interacts with AURKA and facilitate its degradation through the lysosomal pathway to inhibited EMT and metastasis of HCC. AURKA’s specific inhibitor alisertib exerts effective therapeutic effect on liver cancer with low TIALD expression, which might provide a new insight into HCC therapy. Our study uncovers a negative functional loop of METTL16-TIALD-AURKA axis, and identifies a new mechanism for METTL16 mediated m6A-induced decay of TIALD on AURKA signaling in HCC progression, which may provide potential prognostic and therapeutic targets for HCC.
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spelling pubmed-105414122023-10-01 LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation Wang, Yingchao Zhong, Yue Zheng, Xiaoyuan Cheng, Niangmei Yang, Yong Yang, Ye Wang, Fei Zhuang, Qiuyu Huang, Yao Guo, Wuhua Liao, Naishun Yang, Xiaoyu Zhao, Bixing Liu, Xiaolong Cell Death Discov Article The N6-methyladenosine (m6A) RNA methyltransferase METTL16 is an emerging player in RNA modification landscape and responsible for the deposition of m6A in a few transcripts. AURKA (aurora kinase A) has been confirmed as an oncogene in cancer development including hepatocellular carcinoma (HCC). Nevertheless, it remains unclear whether METTL16 mediated m6A modification of lncRNAs can regulate AURKA activation in cancer progression. Here we aimed to investigate the functional links between lncRNAs and the m6A modification in AURKA signaling and HCC progression. Here we show that LncRNA TIALD (transcript that induced AURKA Lysosomal degradation) was down-regulated in HCC tissues by METTL16 mediated m6A methylation to facilitate its RNA degradation, and correlates with poor prognosis. Functional assays reveal that TIALD inhibits HCC metastasis both in vitro and in vivo. Mechanistically, TIALD directly interacts with AURKA and facilitate its degradation through the lysosomal pathway to inhibited EMT and metastasis of HCC. AURKA’s specific inhibitor alisertib exerts effective therapeutic effect on liver cancer with low TIALD expression, which might provide a new insight into HCC therapy. Our study uncovers a negative functional loop of METTL16-TIALD-AURKA axis, and identifies a new mechanism for METTL16 mediated m6A-induced decay of TIALD on AURKA signaling in HCC progression, which may provide potential prognostic and therapeutic targets for HCC. Nature Publishing Group UK 2023-08-26 /pmc/articles/PMC10541412/ /pubmed/37773181 http://dx.doi.org/10.1038/s41420-023-01620-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wang, Yingchao
Zhong, Yue
Zheng, Xiaoyuan
Cheng, Niangmei
Yang, Yong
Yang, Ye
Wang, Fei
Zhuang, Qiuyu
Huang, Yao
Guo, Wuhua
Liao, Naishun
Yang, Xiaoyu
Zhao, Bixing
Liu, Xiaolong
LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation
title LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation
title_full LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation
title_fullStr LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation
title_full_unstemmed LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation
title_short LncRNA TIALD contributes to hepatocellular carcinoma metastasis via inducing AURKA lysosomal degradation
title_sort lncrna tiald contributes to hepatocellular carcinoma metastasis via inducing aurka lysosomal degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10541412/
https://www.ncbi.nlm.nih.gov/pubmed/37773181
http://dx.doi.org/10.1038/s41420-023-01620-w
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