Dataset Information

Long noncoding RNA Gm31629 protects against mucosal damage in experimental colitis via YB-1/E2F pathway.

ABSTRACT: Mucosal healing is a key treatment goal for inflammatory bowel disease, and adequate epithelial regeneration is required for an intact gut epithelium. However, the underlying mechanism for mucosal healing is unclear. Long noncoding RNAs (lncRNAs) have been reported to be involved in the development of inflammatory bowel disease. Here, we report that a lncRNA named Gm31629 decreased in intestinal epithelial cells in response to inflammatory stimulation. Gm31629 deficiency led to exacerbated intestinal inflammation and delayed epithelial regeneration in dextran sulfate sodium-induced (DSS-induced) colitis model. Mechanistically, Gm31629 promoted E2F pathways and cell proliferation by stabilizing Y-box protein 1 (YB-1), thus facilitating epithelial regeneration. Genetic overexpression of Gm31629 protected against DSS-induced colitis in vivo. Theaflavin 3-gallate, a natural compound mimicking Gm31629, alleviated DSS-induced epithelial inflammation and mucosal damage. These results demonstrate an essential role of lncRNA Gm31629 in linking intestinal inflammation and epithelial cell proliferation, providing a potential therapeutic approach to inflammatory bowel disease.

SUBMITTER: Feng X

PROVIDER: S-EPMC8986069 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Long noncoding RNA Gm31629 protects against mucosal damage in experimental colitis via YB-1/E2F pathway.

Feng Xu X Xiao Ye Y He Jian J Yang Mi M Guo Qi Q Su Tian T Huang Yan Y Yi Jun J Li Chang-Jun CJ Luo Xiang-Hang XH Liu Xiao-Wei XW Zhou Hai-Yan HY

JCI insight 20220322 6

Mucosal healing is a key treatment goal for inflammatory bowel disease, and adequate epithelial regeneration is required for an intact gut epithelium. However, the underlying mechanism for mucosal healing is unclear. Long noncoding RNAs (lncRNAs) have been reported to be involved in the development of inflammatory bowel disease. Here, we report that a lncRNA named Gm31629 decreased in intestinal epithelial cells in response to inflammatory stimulation. Gm31629 deficiency led to exacerbated intes ...[more]

PMID: 35143419

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Project description:BackgroundY-box binding factor 1 (YB-1) has been associated with prognosis in many tumor types. Reduced YB-1 expression inhibits tumor cell growth, but the mechanism is unclear.MethodsYB-1 mRNA levels were compared with tumor grade and histology using microarray data from 771 breast cancer patients and with disease-free survival and distant metastasis-free survival using data from 375 of those patients who did not receive adjuvant therapy. Microarrays were further searched for genes that had correlated expression with YB-1 mRNA. Small interfering RNA (siRNA) was used to study the effects of reduced YB-1 expression on growth of three tumor cell lines (MCF-7 breast, HCT116 colon, and A549 lung cancer cells), on tumorigenesis by A549 cells in nude mice, and on global transcription in the three cancer cell lines. Reporter gene assays were used to determine whether YB-1 siRNAs affected the expression of E2F1, and chromatin immunoprecipitation was used to determine whether YB-1 bound to various E2F promoters as well as E2F1-regulated promoters. All P values were from two-sided tests.ResultsYB-1 levels were elevated in more aggressive tumors and were strongly associated with poor disease-free survival and distant metastasis-free survival. YB-1 expression was often associated with the expression of genes with E2F sites in their promoters. Cells expressing YB-1 siRNA grew substantially more slowly than control cells and formed tumors less readily in nude mice. Transcripts that were altered in cancer cell lines with YB-1 siRNA included 32 genes that are components of prognostic gene expression signatures. YB-1 regulated expression of an E2F1 promoter-reporter construct in A549 cells (eg, relative E2F1 promoter activity with control siRNA = 4.04; with YB-1 siRNA = 1.40, difference= -2.64, 95% confidence interval = -3.57 to -1.71, P < .001) and bound to the promoters of several well-defined E2F1 target genes.ConclusionYB-1 expression is associated with the activity of E2F transcription factors and may control tumor cell growth by this mechanism.

Dataset Information

Long noncoding RNA Gm31629 protects against mucosal damage in experimental colitis via YB-1/E2F pathway.

Publications

Long noncoding RNA Gm31629 protects against mucosal damage in experimental colitis via YB-1/E2F pathway.

Similar Datasets

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