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LHFPL3-AS2 lncRNA regulates epithelial polarity and its reduced expression is linked with more severe Crohn Disease

ABSTRACT: LHFPL3-AS2 lncRNA regulates epithelial polarity and its reduced expression is linked with more severe Crohn Disease

PROVIDER: PRJNA895432 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22084646.fastq.gz	Fastqsanger.gz
	SRR22084647.fastq.gz	Fastqsanger.gz
	SRR22084648.fastq.gz	Fastqsanger.gz
	SRR22084649.fastq.gz	Fastqsanger.gz
	SRR22084650.fastq.gz	Fastqsanger.gz

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LHFPL3-AS2 lncRNA regulates epithelial polarity and its reduced expression is linked with more severe Crohn Disease

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Project description:AS2 encode AS2-domain containing protein and may regulate transcription. AS2 is involved in the determination of axes of leaves of Arabidopsis thaliana. Type IB DNA topoisomerase (TOP1α) gene has genetic interaction with AS1 and AS2 and is involved in repression of leaf polarity genes. To know the gene regulation in the leaf development, expression profile among wild-type and as2 mutant treated with and without 10-hydroxyl substituted camptothecin (10H-CPT), a specific TOP1 inhibitor, were compared

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Reduced LHFPL3-AS2 lncRNA expression is linked to altered epithelial polarity and proliferation, and to ileal ulceration in Crohn disease.

Project description: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.

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Analysis of genes regulated by AS1 and AS2

Project description:AS1 and AS2 encode MYB related protein and AS2-domain containing protein, respectively and may regulate transcription. These genes are involved in the determination of axes of leaves of Arabidopsis thaliana. To know the gene regulation in the leaf development, expression profile among wild-type, as1 and as2 mutants and AS2 overexpression plants were compaired. shoot apices from as1-1, as2-1, AS2 overexpressing, and wild type embryos

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