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LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer

Metastasis constitutes one of the major causes of tumor-related death in gastric cancer (GC), and understanding key events in the initiation of this phenotypic switch may provide therapeutic opportunities. Long noncoding RNAs (lncRNAs) are emerging as molecules that play vital roles in tumorigenesis...

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Autores principales: Lu, Yunxin, Meng, Qi, Bai, Long, Wang, Ruobing, Sun, Yong, Li, Jiaqi, Fan, Jun, Tian, Tian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759904/
https://www.ncbi.nlm.nih.gov/pubmed/36528654
http://dx.doi.org/10.1186/s13062-022-00355-5
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author Lu, Yunxin
Meng, Qi
Bai, Long
Wang, Ruobing
Sun, Yong
Li, Jiaqi
Fan, Jun
Tian, Tian
author_facet Lu, Yunxin
Meng, Qi
Bai, Long
Wang, Ruobing
Sun, Yong
Li, Jiaqi
Fan, Jun
Tian, Tian
author_sort Lu, Yunxin
collection PubMed
description Metastasis constitutes one of the major causes of tumor-related death in gastric cancer (GC), and understanding key events in the initiation of this phenotypic switch may provide therapeutic opportunities. Long noncoding RNAs (lncRNAs) are emerging as molecules that play vital roles in tumorigenesis and metastasis. In this study, we aimed to identify metastasis-related lncRNAs in the context of GC. The lncRNAs overexpressed in tumor tissues and positively associated with overall survival were screened out using the TCGA database. qPCR assays in clinical samples showed that LINC00858 was significantly upregulated in GC tissues compared with normal counterparts. Functional analysis suggested that LINC00858 depletion attenuated the migration, and invasion of cancer cells in vitro and suppressed the metastasis of xenografted tumors in vivo. Mechanistically, LINC00858 could interact with the metastasis-associated RAN and stabilize its protein expression by decreasing posttranslational ubiquitination. The transcription factor YY1 could bind to the promoter of LINC00858 to upregulate its expression in GC cells. Moreover, overexpression of YY1 and RAN was positively associated with upregulation of LINC00858 in GC tissues. Our results suggest that LINC00858 might play a role in GC metastasis, and be a diagnostic biomarker and potential therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-022-00355-5.
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spelling pubmed-97599042022-12-19 LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer Lu, Yunxin Meng, Qi Bai, Long Wang, Ruobing Sun, Yong Li, Jiaqi Fan, Jun Tian, Tian Biol Direct Research Metastasis constitutes one of the major causes of tumor-related death in gastric cancer (GC), and understanding key events in the initiation of this phenotypic switch may provide therapeutic opportunities. Long noncoding RNAs (lncRNAs) are emerging as molecules that play vital roles in tumorigenesis and metastasis. In this study, we aimed to identify metastasis-related lncRNAs in the context of GC. The lncRNAs overexpressed in tumor tissues and positively associated with overall survival were screened out using the TCGA database. qPCR assays in clinical samples showed that LINC00858 was significantly upregulated in GC tissues compared with normal counterparts. Functional analysis suggested that LINC00858 depletion attenuated the migration, and invasion of cancer cells in vitro and suppressed the metastasis of xenografted tumors in vivo. Mechanistically, LINC00858 could interact with the metastasis-associated RAN and stabilize its protein expression by decreasing posttranslational ubiquitination. The transcription factor YY1 could bind to the promoter of LINC00858 to upregulate its expression in GC cells. Moreover, overexpression of YY1 and RAN was positively associated with upregulation of LINC00858 in GC tissues. Our results suggest that LINC00858 might play a role in GC metastasis, and be a diagnostic biomarker and potential therapeutic target. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-022-00355-5. BioMed Central 2022-12-17 /pmc/articles/PMC9759904/ /pubmed/36528654 http://dx.doi.org/10.1186/s13062-022-00355-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Lu, Yunxin
Meng, Qi
Bai, Long
Wang, Ruobing
Sun, Yong
Li, Jiaqi
Fan, Jun
Tian, Tian
LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer
title LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer
title_full LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer
title_fullStr LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer
title_full_unstemmed LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer
title_short LINC00858 stabilizes RAN expression and promotes metastasis of gastric cancer
title_sort linc00858 stabilizes ran expression and promotes metastasis of gastric cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9759904/
https://www.ncbi.nlm.nih.gov/pubmed/36528654
http://dx.doi.org/10.1186/s13062-022-00355-5
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