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LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p

BACKGROUND: Increasing evidences have shown that long non-coding RNAs (lncRNAs) display crucial regulatory roles in the occurrence and development of numerous diseases. However, the function and underlying mechanisms of lncRNAs in hypertrophy of ligamentum flavum (HLF) have not been report. METHODS:...

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Autores principales: Cao, Yanlin, Li, Jianjun, Qiu, Sujun, Ni, Songjia, Duan, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10207765/
https://www.ncbi.nlm.nih.gov/pubmed/37226251
http://dx.doi.org/10.1186/s13062-023-00383-9
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author Cao, Yanlin
Li, Jianjun
Qiu, Sujun
Ni, Songjia
Duan, Yang
author_facet Cao, Yanlin
Li, Jianjun
Qiu, Sujun
Ni, Songjia
Duan, Yang
author_sort Cao, Yanlin
collection PubMed
description BACKGROUND: Increasing evidences have shown that long non-coding RNAs (lncRNAs) display crucial regulatory roles in the occurrence and development of numerous diseases. However, the function and underlying mechanisms of lncRNAs in hypertrophy of ligamentum flavum (HLF) have not been report. METHODS: The integrated analysis of lncRNAs sequencing, bioinformatics analysis and real-time quantitative PCR were used to identify the key lncRNAs involved in HLF progression. Gain- and loss-function experiments were used to explore the functions of lncRNA X inactive specific transcript (XIST) in HLF. Mechanistically, bioinformatics binding site analysis, RNA pull-down, dual-luciferase reporter assay, and rescue experiments were utilized to investigate the mechanism by which XIST acts as a molecular sponge of miR-302b-3p to regulate VEGFA-mediated autophagy. RESULTS: We identified that XIST was outstandingly upregulated in HLF tissues and cells. Moreover, the up-regulation of XIST strongly correlated with the thinness and fibrosis degree of LF in LSCS patients. Functionally, knockdown of XIST drastically inhibited proliferation, anti-apoptosis, fibrosis and autophagy of HLF cells in vitro and suppressed hypertrophy and fibrosis of LF tissues in vivo. Intestinally, we uncovered that overexpression of XIST significantly promoted proliferation, anti-apoptosis and fibrosis ability of HLF cells by activating autophagy. Mechanistic studies illustrated that XIST directly medullated the VEGFA-mediated autophagy through sponging miR-302b-3p, thereby enhancing the development and progression of HLF. CONCLUSION: Our findings highlighted that the XIST/miR-302b-3p/VEGFA-mediated autophagy axis is involved in development and progression of HLF. At the same time, this study will complement the blank of lncRNA expression profiles in HLF, which laid the foundation for further exploration of the relationship between lncRNAs and HLF in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00383-9.
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spelling pubmed-102077652023-05-25 LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p Cao, Yanlin Li, Jianjun Qiu, Sujun Ni, Songjia Duan, Yang Biol Direct Research BACKGROUND: Increasing evidences have shown that long non-coding RNAs (lncRNAs) display crucial regulatory roles in the occurrence and development of numerous diseases. However, the function and underlying mechanisms of lncRNAs in hypertrophy of ligamentum flavum (HLF) have not been report. METHODS: The integrated analysis of lncRNAs sequencing, bioinformatics analysis and real-time quantitative PCR were used to identify the key lncRNAs involved in HLF progression. Gain- and loss-function experiments were used to explore the functions of lncRNA X inactive specific transcript (XIST) in HLF. Mechanistically, bioinformatics binding site analysis, RNA pull-down, dual-luciferase reporter assay, and rescue experiments were utilized to investigate the mechanism by which XIST acts as a molecular sponge of miR-302b-3p to regulate VEGFA-mediated autophagy. RESULTS: We identified that XIST was outstandingly upregulated in HLF tissues and cells. Moreover, the up-regulation of XIST strongly correlated with the thinness and fibrosis degree of LF in LSCS patients. Functionally, knockdown of XIST drastically inhibited proliferation, anti-apoptosis, fibrosis and autophagy of HLF cells in vitro and suppressed hypertrophy and fibrosis of LF tissues in vivo. Intestinally, we uncovered that overexpression of XIST significantly promoted proliferation, anti-apoptosis and fibrosis ability of HLF cells by activating autophagy. Mechanistic studies illustrated that XIST directly medullated the VEGFA-mediated autophagy through sponging miR-302b-3p, thereby enhancing the development and progression of HLF. CONCLUSION: Our findings highlighted that the XIST/miR-302b-3p/VEGFA-mediated autophagy axis is involved in development and progression of HLF. At the same time, this study will complement the blank of lncRNA expression profiles in HLF, which laid the foundation for further exploration of the relationship between lncRNAs and HLF in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-023-00383-9. BioMed Central 2023-05-24 /pmc/articles/PMC10207765/ /pubmed/37226251 http://dx.doi.org/10.1186/s13062-023-00383-9 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 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
Cao, Yanlin
Li, Jianjun
Qiu, Sujun
Ni, Songjia
Duan, Yang
LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p
title LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p
title_full LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p
title_fullStr LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p
title_full_unstemmed LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p
title_short LncRNA XIST facilitates hypertrophy of ligamentum flavum by activating VEGFA-mediated autophagy through sponging miR-302b-3p
title_sort lncrna xist facilitates hypertrophy of ligamentum flavum by activating vegfa-mediated autophagy through sponging mir-302b-3p
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10207765/
https://www.ncbi.nlm.nih.gov/pubmed/37226251
http://dx.doi.org/10.1186/s13062-023-00383-9
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