Reduced LHFPL3-AS2 lncRNA expression is linked to altered epithelial polarity and proliferation, and to ileal ulceration in Crohn disease.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 Nov 2023
22 Nov 2023
Historique:
received:
04
08
2023
accepted:
21
11
2023
medline:
24
11
2023
pubmed:
23
11
2023
entrez:
22
11
2023
Statut:
epublish
Résumé
Disruption of intestinal epithelial functions is linked to Crohn disease (CD) pathogenesis. We identified a widespread reduction in the expression of long non-coding RNAs (lncRNAs) including LHFPL3-AS2 in the treatment-naïve CD ileum of the RISK pediatric cohort. We validated the reduction of LHFPL3-AS2 in adult CD and noted a further reduction in patients with more severe CD from the RISK cohort. LHFPL3-AS2 knockdown in Caco-2 cells robustly affected epithelial monolayer morphogenesis with markedly reduced confluency and spreading, showing atypical rounding, and clumping. mRNA-seq analysis of LHFPL3-AS2 knockdown cells highlighted the reduction of genes and pathways linked with apical polarity, actin bundles, morphogenesis, and the b-catenin-TCF4 complex. LHFPL3-AS2 knockdown significantly reduced the ability of cells to form an internal lumen within the 3-dimensional (3D) cyst model, with mislocalization of actin and adherent and tight junction proteins, affecting epithelial polarity. LHFPL3-AS2 knockdown also resulted in defective mitotic spindle formation and consequent reduction in epithelial proliferation. Altogether, we show that LHFPL3-AS2 reduction affects epithelial morphogenesis, polarity, mitotic spindle formation, and proliferation, which are key processes in maintaining epithelial homeostasis in CD. Reduced expression of LHFPL3-AS2 in CD patients and its further reduction with ileal ulceration outcome, emphasizes its significance in this context.
Identifiants
pubmed: 37993670
doi: 10.1038/s41598-023-47997-7
pii: 10.1038/s41598-023-47997-7
pmc: PMC10665440
doi:
Substances chimiques
RNA, Long Noncoding
0
Actins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
20513Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : European Research Council
ID : 758313
Pays : International
Informations de copyright
© 2023. The Author(s).
Références
Inflamm Bowel Dis. 2018 Jan 18;24(2):346-360
pubmed: 29361088
Cold Spring Harb Perspect Biol. 2017 Jul 5;9(7):
pubmed: 28213466
Nat Cell Biol. 2007 Feb;9(2):160-70
pubmed: 17330329
Mol Biol Cell. 2016 Feb 15;27(4):617-26
pubmed: 26680741
J Cell Biol. 1999 Feb 22;144(4):687-99
pubmed: 10037790
Oncol Rep. 2020 Dec;44(6):2503-2516
pubmed: 33125127
J Cell Sci. 2006 Oct 15;119(Pt 20):4155-63
pubmed: 17038542
Int J Oncol. 2011 May;38(5):1365-73
pubmed: 21369697
EMBO J. 2012 Nov 28;31(23):4415-27
pubmed: 23103768
Mol Cell Proteomics. 2014 Feb;13(2):397-406
pubmed: 24309898
J Physiol Biochem. 2008 Dec;64(4):377-82
pubmed: 19391463
J Cell Biol. 2001 May 28;153(5):1049-60
pubmed: 11381089
Int J Radiat Oncol Biol Phys. 1992;22(3):613-7
pubmed: 1346533
Biol Bull. 2008 Jun;214(3):218-32
pubmed: 18574100
J Cell Biol. 2005 Dec 19;171(6):1061-71
pubmed: 16344308
J Clin Invest. 2014 Jul;124(7):2947-62
pubmed: 24892806
Gastroenterology. 2021 Dec;161(6):1924-1939
pubmed: 34478742
Nucleic Acids Res. 2010 Jul;38(Web Server issue):W96-102
pubmed: 20484371
J Cell Biol. 2008 Nov 17;183(4):625-33
pubmed: 19001128
Cell. 2008 Nov 28;135(5):865-78
pubmed: 19041750
Gastroenterology. 1989 Mar;96(3):736-49
pubmed: 2914637
Traffic. 2018 May 16;:
pubmed: 29766620
J Cell Physiol. 2008 Apr;215(1):182-91
pubmed: 17960592
JCI Insight. 2023 Jul 24;8(14):
pubmed: 37261910
Trends Genet. 2019 Dec;35(12):892-902
pubmed: 31662190
Curr Biol. 2003 Aug 5;13(15):R614-24
pubmed: 12906817
J Clin Invest. 2014 Aug;124(8):3617-33
pubmed: 25003194
Cell Mol Gastroenterol Hepatol. 2022;14(5):1053-1076
pubmed: 35944892
Cell Mol Life Sci. 2013 Dec;70(24):4785-94
pubmed: 23880895
Adv Exp Med Biol. 2005;570:393-421
pubmed: 18727509
J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):254-260
pubmed: 27050050
Gut. 2022 Jan 12;:
pubmed: 35022268
Nat Rev Mol Cell Biol. 2014 Apr;15(4):225-42
pubmed: 24651541
Clin Rev Allergy Immunol. 2021 Apr;60(2):164-174
pubmed: 32474815
J Cell Biol. 2005 Jan 17;168(2):221-32
pubmed: 15642749
Genome Res. 2003 Nov;13(11):2498-504
pubmed: 14597658
J Cell Biol. 1994 Sep;126(6):1509-26
pubmed: 8089182
Mol Cell Biol. 2016 Apr 15;36(9):1332-41
pubmed: 26884465
Cancer Res. 2018 Oct 15;78(20):5877-5890
pubmed: 30185552
Int J Oncol. 2008 Feb;32(2):377-85
pubmed: 18202760
J Biol Chem. 2011 Apr 8;286(14):12461-74
pubmed: 21300793
Oncogene. 2011 Apr 21;30(16):1956-62
pubmed: 21151178
J Cell Biol. 1994 Jun;125(6):1327-40
pubmed: 8207061
Gastroenterology. 2018 Feb;154(3):585-598
pubmed: 29031501
Nat Rev Gastroenterol Hepatol. 2017 Jan;14(1):9-21
pubmed: 27848962
Nucleic Acids Res. 2021 Jan 8;49(D1):D605-D612
pubmed: 33237311
Gastroenterology. 2013 Oct;145(4):808-19
pubmed: 23792201
Am J Gastroenterol. 2002 Apr;97(4):947-53
pubmed: 12003431
J Cell Biol. 1992 Feb;116(4):989-96
pubmed: 1734027
Nature. 2008 Jul 3;454(7200):126-30
pubmed: 18509338
Gut. 1989 Jul;30(7):983-9
pubmed: 2668130
J Crohns Colitis. 2023 Jun 16;17(6):960-971
pubmed: 36655602
Cancer Sci. 2006 Nov;97(11):1217-25
pubmed: 16965391
Curr Biol. 2015 Feb 16;25(4):R162-71
pubmed: 25689915
J Cell Sci. 2009 Dec 1;122(Pt 23):4253-66
pubmed: 19923269
Nat Methods. 2012 Nov;9(11):1069-76
pubmed: 23132118
Genes Dev. 2012 Dec 15;26(24):2709-23
pubmed: 23249734
Int Rev Cytol. 2003;226:127-64
pubmed: 12921237
Microsc Res Tech. 2000 May 15;49(4):353-62
pubmed: 10820519
Gastroenterology. 2007 Aug;133(2):412-22
pubmed: 17681162
J Cell Biol. 2001 Sep 17;154(6):1185-96
pubmed: 11564756
Cancer Lett. 2022 Apr 10;531:1-13
pubmed: 35101541
Annu Rev Physiol. 2020 Feb 10;82:251-273
pubmed: 31618602
Traffic. 2000 Jan;1(1):76-83
pubmed: 11208062
Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11
pubmed: 19465376
PLoS Genet. 2013 Mar;9(3):e1003368
pubmed: 23555285
J Biol Chem. 2001 Jan 12;276(2):875-83
pubmed: 11035016
J Cell Biol. 1998 Mar 9;140(5):1039-53
pubmed: 9490718