The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis
The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1168693/full |
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| author | Tianyun Long Juan E. Hernandez Shengyun Ma Scarlet Steele Claire Luo Yuxin Li Qinghong Xie Francesca Telese Bing Zhou Bing Zhou Wendy Jia Men Huang |
| author_facet | Tianyun Long Juan E. Hernandez Shengyun Ma Scarlet Steele Claire Luo Yuxin Li Qinghong Xie Francesca Telese Bing Zhou Bing Zhou Wendy Jia Men Huang |
| author_sort | Tianyun Long |
| collection | DOAJ |
| description | The long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development remain unexplored. Here, we report that MALAT1 regulates host anti-microbial response gene expression and the composition of mucosal-associated microbial communities in a region-specific manner. In the APC mutant mouse model of intestine tumorigenesis, knocking out MALAT1 results in higher polyp counts in the small intestine and colon. Interestingly, intestine polyps that developed in the absence of MALAT1 were smaller in size. These findings highlight the unexpected bivalent role of MALAT1 in restricting and promoting cancer progression at different disease stages. Among the 30 MALAT1-targets shared by both the small intestine and colon, ZNF638 and SENP8 levels are predictive of colon adenoma patient overall survival and disease-free survival. Genomic assays further revealed that MALAT1 modulates intestinal target expression and splicing through both direct and indirect mechanisms. This study expands the role of lncRNAs in regulating intestine homeostasis, microbial communities, and cancer pathogenesis. |
| first_indexed | 2024-03-13T08:18:56Z |
| format | Article |
| id | doaj.art-abc12fda81c941f9a9f78d2b3cac61b3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-13T08:18:56Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-abc12fda81c941f9a9f78d2b3cac61b32023-05-31T10:55:51ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-05-011110.3389/fcell.2023.11686931168693The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposisTianyun Long0Juan E. Hernandez1Shengyun Ma2Scarlet Steele3Claire Luo4Yuxin Li5Qinghong Xie6Francesca Telese7Bing Zhou8Bing Zhou9Wendy Jia Men Huang10Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesDepartment of Psychiatry, University of California San Diego, La Jolla, CA, United StatesState Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology Chinese Academy of Sciences, Beijing, ChinaBeijing Institute for Stem Cell and Regenerative Medicine, Beijing, ChinaDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, United StatesThe long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) maintains the integrity of the intestinal epithelial barrier and regulates local inflammation. However, its influences on intestinal microbial communities and tissue susceptibility to cancer development remain unexplored. Here, we report that MALAT1 regulates host anti-microbial response gene expression and the composition of mucosal-associated microbial communities in a region-specific manner. In the APC mutant mouse model of intestine tumorigenesis, knocking out MALAT1 results in higher polyp counts in the small intestine and colon. Interestingly, intestine polyps that developed in the absence of MALAT1 were smaller in size. These findings highlight the unexpected bivalent role of MALAT1 in restricting and promoting cancer progression at different disease stages. Among the 30 MALAT1-targets shared by both the small intestine and colon, ZNF638 and SENP8 levels are predictive of colon adenoma patient overall survival and disease-free survival. Genomic assays further revealed that MALAT1 modulates intestinal target expression and splicing through both direct and indirect mechanisms. This study expands the role of lncRNAs in regulating intestine homeostasis, microbial communities, and cancer pathogenesis.https://www.frontiersin.org/articles/10.3389/fcell.2023.1168693/fulllong non-coding RNAMALAT1intestinal cancerintestine microbesintestine epithelial cells |
| spellingShingle | Tianyun Long Juan E. Hernandez Shengyun Ma Scarlet Steele Claire Luo Yuxin Li Qinghong Xie Francesca Telese Bing Zhou Bing Zhou Wendy Jia Men Huang The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis Frontiers in Cell and Developmental Biology long non-coding RNA MALAT1 intestinal cancer intestine microbes intestine epithelial cells |
| title | The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis |
| title_full | The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis |
| title_fullStr | The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis |
| title_full_unstemmed | The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis |
| title_short | The long non-coding RNA MALAT1 regulates intestine host-microbe interactions and polyposis |
| title_sort | long non coding rna malat1 regulates intestine host microbe interactions and polyposis |
| topic | long non-coding RNA MALAT1 intestinal cancer intestine microbes intestine epithelial cells |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1168693/full |
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