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LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription

Rationale: Tumor metastasis is the main cause for cancer-related death. However, the driving molecules of metastasis remain largely unknown. Here, we aim to identify long non-coding RNAs (lncRNAs) critical for human hepatocellular carcinoma (HCC) metastasis. Methods: Microarrays were used to screen...

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Autores principales: Kang, Chun Lan, Qi, Bing, Cai, Qian Qian, Fu, Li Sheng, Yang, Ying, Tang, Chang, Zhu, Ping, Chen, Qi Wen, Pan, Jing, Chen, Mei Hua, Wu, Xing Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599657/
https://www.ncbi.nlm.nih.gov/pubmed/31285770
http://dx.doi.org/10.7150/thno.32854
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author Kang, Chun Lan
Qi, Bing
Cai, Qian Qian
Fu, Li Sheng
Yang, Ying
Tang, Chang
Zhu, Ping
Chen, Qi Wen
Pan, Jing
Chen, Mei Hua
Wu, Xing Zhong
author_facet Kang, Chun Lan
Qi, Bing
Cai, Qian Qian
Fu, Li Sheng
Yang, Ying
Tang, Chang
Zhu, Ping
Chen, Qi Wen
Pan, Jing
Chen, Mei Hua
Wu, Xing Zhong
author_sort Kang, Chun Lan
collection PubMed
description Rationale: Tumor metastasis is the main cause for cancer-related death. However, the driving molecules of metastasis remain largely unknown. Here, we aim to identify long non-coding RNAs (lncRNAs) critical for human hepatocellular carcinoma (HCC) metastasis. Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in sulfatide-treated cells. Mass spectrometry, protein arrays, and RNA pull-down experiments were used to identify proteins that interacted with lncRNA. Epigenetic analysis was used to study lncRNA-mediated regulation mechanisms. Results: We identified lncRNA AY927503 (AY) as a metastasis-associated molecule that was highly expressed in human hepatocellular carcinoma (HCC) and correlated with metastatic events and poor prognosis in patients with HCC. AY promoted HCC cell migration, stemness, 5-fluorouracil resistance, and metastasis in mice. However, knockdown of integrin αV (ITGAV) abolished AY-stimulated migration, cell viability in HCC cells or tube formation. AY strongly promoted ITGAV transcription and αVβ3 expression by interacting with the ITGAV promoter specifically and stimulating its activity. AY was identified to interact with histone 1FX (H1FX), but deletion of the central domain of AY (AY∆371-522) abolished H1FX binding and ITGAV promoter stimulation. AY significantly enriched H3K4Me3 and acH3K9/14 but reduced H3K27Me3 and H1FX occupancy on the ITGAV promoter, which remodeled chromatin structures for RNA polymerase II recruitment. Knockdown of H1FX abrogated ITGAV transcription stimulated by AY. Conclusions: Our findings suggested that lncRNA AY promoted HCC metastasis via induction of chromatin modification for ITGAV transcription as a pioneer factor and was a potential molecular signature for metastasis or poor prognosis in patients with HCC.
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spelling pubmed-65996572019-07-08 LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription Kang, Chun Lan Qi, Bing Cai, Qian Qian Fu, Li Sheng Yang, Ying Tang, Chang Zhu, Ping Chen, Qi Wen Pan, Jing Chen, Mei Hua Wu, Xing Zhong Theranostics Research Paper Rationale: Tumor metastasis is the main cause for cancer-related death. However, the driving molecules of metastasis remain largely unknown. Here, we aim to identify long non-coding RNAs (lncRNAs) critical for human hepatocellular carcinoma (HCC) metastasis. Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in sulfatide-treated cells. Mass spectrometry, protein arrays, and RNA pull-down experiments were used to identify proteins that interacted with lncRNA. Epigenetic analysis was used to study lncRNA-mediated regulation mechanisms. Results: We identified lncRNA AY927503 (AY) as a metastasis-associated molecule that was highly expressed in human hepatocellular carcinoma (HCC) and correlated with metastatic events and poor prognosis in patients with HCC. AY promoted HCC cell migration, stemness, 5-fluorouracil resistance, and metastasis in mice. However, knockdown of integrin αV (ITGAV) abolished AY-stimulated migration, cell viability in HCC cells or tube formation. AY strongly promoted ITGAV transcription and αVβ3 expression by interacting with the ITGAV promoter specifically and stimulating its activity. AY was identified to interact with histone 1FX (H1FX), but deletion of the central domain of AY (AY∆371-522) abolished H1FX binding and ITGAV promoter stimulation. AY significantly enriched H3K4Me3 and acH3K9/14 but reduced H3K27Me3 and H1FX occupancy on the ITGAV promoter, which remodeled chromatin structures for RNA polymerase II recruitment. Knockdown of H1FX abrogated ITGAV transcription stimulated by AY. Conclusions: Our findings suggested that lncRNA AY promoted HCC metastasis via induction of chromatin modification for ITGAV transcription as a pioneer factor and was a potential molecular signature for metastasis or poor prognosis in patients with HCC. Ivyspring International Publisher 2019-06-09 /pmc/articles/PMC6599657/ /pubmed/31285770 http://dx.doi.org/10.7150/thno.32854 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Kang, Chun Lan
Qi, Bing
Cai, Qian Qian
Fu, Li Sheng
Yang, Ying
Tang, Chang
Zhu, Ping
Chen, Qi Wen
Pan, Jing
Chen, Mei Hua
Wu, Xing Zhong
LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription
title LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription
title_full LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription
title_fullStr LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription
title_full_unstemmed LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription
title_short LncRNA AY promotes hepatocellular carcinoma metastasis by stimulating ITGAV transcription
title_sort lncrna ay promotes hepatocellular carcinoma metastasis by stimulating itgav transcription
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6599657/
https://www.ncbi.nlm.nih.gov/pubmed/31285770
http://dx.doi.org/10.7150/thno.32854
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