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CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells

BACKGROUND: RNA binding proteins (RBPs)-mediated regulation plays important roles in many eye diseases, including the canonical RBP CELF1 in cataract. While the definite molecular regulatory mechanisms of CELF1 on cataract still remain elusive. METHODS: In this study, we overexpressed CELF1 in human...

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Autores principales: Xiao, Jun, Tian, Xin, Jin, Siyan, He, Yanhui, Song, Meijiao, Zou, He
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922852/
https://www.ncbi.nlm.nih.gov/pubmed/35287612
http://dx.doi.org/10.1186/s12886-022-02344-8
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author Xiao, Jun
Tian, Xin
Jin, Siyan
He, Yanhui
Song, Meijiao
Zou, He
author_facet Xiao, Jun
Tian, Xin
Jin, Siyan
He, Yanhui
Song, Meijiao
Zou, He
author_sort Xiao, Jun
collection PubMed
description BACKGROUND: RNA binding proteins (RBPs)-mediated regulation plays important roles in many eye diseases, including the canonical RBP CELF1 in cataract. While the definite molecular regulatory mechanisms of CELF1 on cataract still remain elusive. METHODS: In this study, we overexpressed CELF1 in human cultured lens epithelial SRA01/04 cells and applied whole transcriptome sequencing (RNA-seq) method to analyze the global differences mediated by CELF1. We then analyzed public RNA-seq and CELF1-RNA interactome data to decipher the underlying mechanisms. RESULTS: The results showed that transcriptome profile was globally changed by CELF1 overexpression (CELF1-OE). Functional analysis revealed CELF1 specifically increased the expression of genes in extracellular matrix disassembly, extracellular matrix organization, and proteolysis, which could be classified into matrix metalloproteinases (MMPs) family. This finding was also validated by RT-qPCR and public mouse early embryonic lens data. Integrating analysis with public CELF1-RNA interactome data revealed that no obvious CELF1-binding peak was found on the transcripts of these genes, indicating an indirectly regulatory role of CELF1 in lens epithelial cells. CONCLUSIONS: Our study demonstrated that CELF1-OE promotes transcriptional level of MMP genes; and this regulation may be completed by other ways except for binding to RNA targets. These results suggest that CELF1-OE is implicated in the development of lens, which is associated with cataract and expands our understanding of CELF1 regulatory roles as an RNA binding protein. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-022-02344-8.
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spelling pubmed-89228522022-03-22 CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells Xiao, Jun Tian, Xin Jin, Siyan He, Yanhui Song, Meijiao Zou, He BMC Ophthalmol Research BACKGROUND: RNA binding proteins (RBPs)-mediated regulation plays important roles in many eye diseases, including the canonical RBP CELF1 in cataract. While the definite molecular regulatory mechanisms of CELF1 on cataract still remain elusive. METHODS: In this study, we overexpressed CELF1 in human cultured lens epithelial SRA01/04 cells and applied whole transcriptome sequencing (RNA-seq) method to analyze the global differences mediated by CELF1. We then analyzed public RNA-seq and CELF1-RNA interactome data to decipher the underlying mechanisms. RESULTS: The results showed that transcriptome profile was globally changed by CELF1 overexpression (CELF1-OE). Functional analysis revealed CELF1 specifically increased the expression of genes in extracellular matrix disassembly, extracellular matrix organization, and proteolysis, which could be classified into matrix metalloproteinases (MMPs) family. This finding was also validated by RT-qPCR and public mouse early embryonic lens data. Integrating analysis with public CELF1-RNA interactome data revealed that no obvious CELF1-binding peak was found on the transcripts of these genes, indicating an indirectly regulatory role of CELF1 in lens epithelial cells. CONCLUSIONS: Our study demonstrated that CELF1-OE promotes transcriptional level of MMP genes; and this regulation may be completed by other ways except for binding to RNA targets. These results suggest that CELF1-OE is implicated in the development of lens, which is associated with cataract and expands our understanding of CELF1 regulatory roles as an RNA binding protein. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-022-02344-8. BioMed Central 2022-03-14 /pmc/articles/PMC8922852/ /pubmed/35287612 http://dx.doi.org/10.1186/s12886-022-02344-8 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
Xiao, Jun
Tian, Xin
Jin, Siyan
He, Yanhui
Song, Meijiao
Zou, He
CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells
title CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells
title_full CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells
title_fullStr CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells
title_full_unstemmed CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells
title_short CELF1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells
title_sort celf1 promotes matrix metalloproteinases gene expression at transcriptional level in lens epithelial cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922852/
https://www.ncbi.nlm.nih.gov/pubmed/35287612
http://dx.doi.org/10.1186/s12886-022-02344-8
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