Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4

<h3>Background and aims</h3><p dir="ltr">The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as...

Full description

Saved in:
Bibliographic Details
Main Author: Khaoula Errafii (10914446) (author)
Other Authors: Neyla S. Al-Akl (10914449) (author), Olfa Khalifa (10914452) (author), Abdelilah Arredouani (14070786) (author)
Published: 2021
Subjects:
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1864513541050990592
author Khaoula Errafii (10914446)
author2 Neyla S. Al-Akl (10914449)
Olfa Khalifa (10914452)
Abdelilah Arredouani (14070786)
author2_role author
author
author
author_facet Khaoula Errafii (10914446)
Neyla S. Al-Akl (10914449)
Olfa Khalifa (10914452)
Abdelilah Arredouani (14070786)
author_role author
dc.creator.none.fl_str_mv Khaoula Errafii (10914446)
Neyla S. Al-Akl (10914449)
Olfa Khalifa (10914452)
Abdelilah Arredouani (14070786)
dc.date.none.fl_str_mv 2021-06-02T18:00:00Z
dc.identifier.none.fl_str_mv 10.1186/s12967-021-02885-4
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Comprehensive_analysis_of_LncRNAs_expression_profiles_in_an_in_vitro_model_of_steatosis_treated_with_Exendin-4/21598452
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Medical biochemistry and metabolomics
General Biochemistry, Genetics and Molecular Biology
General Medicine
dc.title.none.fl_str_mv Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Background and aims</h3><p dir="ltr">The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro.</p><h3>Methods</h3><p dir="ltr">Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs.</p><h3>Results</h3><p dir="ltr">We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways.</p><h3>Conclusion</h3><p dir="ltr">Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Translational Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1186/s12967-021-02885-4" target="_blank">http://dx.doi.org/10.1186/s12967-021-02885-4</a></p>
eu_rights_str_mv openAccess
id Manara2_322a235324460a4f43140843d85ea46a
identifier_str_mv 10.1186/s12967-021-02885-4
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/21598452
publishDate 2021
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4Khaoula Errafii (10914446)Neyla S. Al-Akl (10914449)Olfa Khalifa (10914452)Abdelilah Arredouani (14070786)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesMedical biochemistry and metabolomicsGeneral Biochemistry, Genetics and Molecular BiologyGeneral Medicine<h3>Background and aims</h3><p dir="ltr">The hallmark of non-alcoholic fatty liver disease (NAFLD) is the excessive hepatic lipid accumulation. Currently, no pharmacotherapy exists for NAFLD. However, the glucagon-like peptide-1 receptor agonists have recently emerged as potential therapeutics. Here, we sought to identify the long non-coding RNAs (LncRNAs) associated with the steatosis improvement induced by the GLP-1R agonist Exendin-4 (Ex-4) in vitro.</p><h3>Methods</h3><p dir="ltr">Steatosis was induced in HepG2 cells with oleic acid. The transcriptomic profiling was performed using total RNA extracted from untreated, steatotic, and Ex-4-treated steatotic cells. We validated a subset of differentially expressed LncRNAs with qRT-PCR and identified the most significantly enriched cellular functions associated with the relevant LncRNAs.</p><h3>Results</h3><p dir="ltr">We confirm that Ex-4 improves steatosis in HepG2 cells. We found 379 and 180 differentially expressed LncRNAs between untreated and steatotic cells and between steatotic and Ex-4-treated steatotic cells, respectively. Interestingly, 22 upregulated LncRNAs in steatotic cells became downregulated with Ex-4 exposure, while 50 downregulated LncRNAs in steatotic cells became upregulated in the presence of Ex-4. Although some LncRNAs, such as MALAT1, H19, and NEAT1, were previously associated with NAFLD, the association of others with steatosis and the positive effect of Ex-4 is being reported for the first time. Functional enrichment analysis identified many critical pathways, including fatty acid and pyruvate metabolism, and insulin, PPAR, Wnt, TGF-β, mTOR, VEGF, NOD-like, and Toll-like receptors signaling pathways.</p><h3>Conclusion</h3><p dir="ltr">Our results suggest that LncRNAs may play essential roles in the mechanisms underlying steatosis improvement in response to GLP-1R agonists and warrant further functional studies.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Translational Medicine<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1186/s12967-021-02885-4" target="_blank">http://dx.doi.org/10.1186/s12967-021-02885-4</a></p>2021-06-02T18:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1186/s12967-021-02885-4https://figshare.com/articles/journal_contribution/Comprehensive_analysis_of_LncRNAs_expression_profiles_in_an_in_vitro_model_of_steatosis_treated_with_Exendin-4/21598452CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215984522021-06-02T18:00:00Z
spellingShingle Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
Khaoula Errafii (10914446)
Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Medical biochemistry and metabolomics
General Biochemistry, Genetics and Molecular Biology
General Medicine
status_str publishedVersion
title Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
title_full Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
title_fullStr Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
title_full_unstemmed Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
title_short Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
title_sort Comprehensive analysis of LncRNAs expression profiles in an in vitro model of steatosis treated with Exendin-4
topic Biological sciences
Biochemistry and cell biology
Biomedical and clinical sciences
Medical biochemistry and metabolomics
General Biochemistry, Genetics and Molecular Biology
General Medicine