G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells
Summary: The cancer-promoting lncRNA HOTAIR has multiple isoforms. Which isoform of HOTAIR accounts for its expression and functions in cancer is unknown. Unlike HOTAIR’s canonical intergenic isoform NR_003716 (HOTAIR-C), the novel isoform NR_047517 (HOTAIR-N) forms an overlapping antisense transcri...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223026366 |
| _version_ | 1797388785510514688 |
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| author | Xiaohan Qu Zhen Lin Janarthanan Jayawickramarajah John S. Alsager Emily Schmidt Kenneth P. Nephew Fang Fang Shankar Balasubramanian Bin Shan |
| author_facet | Xiaohan Qu Zhen Lin Janarthanan Jayawickramarajah John S. Alsager Emily Schmidt Kenneth P. Nephew Fang Fang Shankar Balasubramanian Bin Shan |
| author_sort | Xiaohan Qu |
| collection | DOAJ |
| description | Summary: The cancer-promoting lncRNA HOTAIR has multiple isoforms. Which isoform of HOTAIR accounts for its expression and functions in cancer is unknown. Unlike HOTAIR’s canonical intergenic isoform NR_003716 (HOTAIR-C), the novel isoform NR_047517 (HOTAIR-N) forms an overlapping antisense transcription locus with HOXC11. We identified HOTAIR-N as the dominant isoform that regulates the gene expression programs and networks for cell proliferation, survival, and death in cancer cells. The CpG island in the HOTAIR-N promoter was marked with epigenetic markers for active transcription. We identified a G-quadruplex (G4) motif rich region in the HOTAIR-N CpG island. Our findings indicate that G4s in HOTAIR-N CpG island is critical for expression of HOTAIR-N in cancer cells. Disruption of G4 may represent a novel therapeutic approach for cancer. The transcriptomes regulated by HOTAIR-N and Bloom in cancer cells as provided herein are important resources for the exploration of lncRNA, DNA helicases, and G4 in cancer. |
| first_indexed | 2024-03-08T22:45:51Z |
| format | Article |
| id | doaj.art-fe73e8f106554b4b99f7ce44e4de26b0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T22:45:51Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-fe73e8f106554b4b99f7ce44e4de26b02023-12-17T06:41:11ZengElsevieriScience2589-00422023-12-012612108559G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cellsXiaohan Qu0Zhen Lin1Janarthanan Jayawickramarajah2John S. Alsager3Emily Schmidt4Kenneth P. Nephew5Fang Fang6Shankar Balasubramanian7Bin Shan8Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, China; Corresponding authorDeparmtent of Pathology, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Chemistry, Tulane University, New Orleans, LA 70118, USADepartment of Biomedical Sciences, Elson S Floyd College of Medicine, Washington State University, Spokane, WA 99202, USADepartment of Chemistry, Tulane University, New Orleans, LA 70118, USAMedical Sciences, Cell and Molecular Cancer Biology Program, Indiana University School of Medicine, Bloomington, IN 47405, USAMedical Sciences, Cell and Molecular Cancer Biology Program, Indiana University School of Medicine, Bloomington, IN 47405, USADepartment of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK; Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UKDepartment of Biomedical Sciences, Elson S Floyd College of Medicine, Washington State University, Spokane, WA 99202, USASummary: The cancer-promoting lncRNA HOTAIR has multiple isoforms. Which isoform of HOTAIR accounts for its expression and functions in cancer is unknown. Unlike HOTAIR’s canonical intergenic isoform NR_003716 (HOTAIR-C), the novel isoform NR_047517 (HOTAIR-N) forms an overlapping antisense transcription locus with HOXC11. We identified HOTAIR-N as the dominant isoform that regulates the gene expression programs and networks for cell proliferation, survival, and death in cancer cells. The CpG island in the HOTAIR-N promoter was marked with epigenetic markers for active transcription. We identified a G-quadruplex (G4) motif rich region in the HOTAIR-N CpG island. Our findings indicate that G4s in HOTAIR-N CpG island is critical for expression of HOTAIR-N in cancer cells. Disruption of G4 may represent a novel therapeutic approach for cancer. The transcriptomes regulated by HOTAIR-N and Bloom in cancer cells as provided herein are important resources for the exploration of lncRNA, DNA helicases, and G4 in cancer.http://www.sciencedirect.com/science/article/pii/S2589004223026366Molecular StructureEpigeneticsCancerTranscriptomics |
| spellingShingle | Xiaohan Qu Zhen Lin Janarthanan Jayawickramarajah John S. Alsager Emily Schmidt Kenneth P. Nephew Fang Fang Shankar Balasubramanian Bin Shan G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells iScience Molecular Structure Epigenetics Cancer Transcriptomics |
| title | G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells |
| title_full | G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells |
| title_fullStr | G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells |
| title_full_unstemmed | G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells |
| title_short | G-quadruplex is critical to epigenetic activation of the lncRNA HOTAIR in cancer cells |
| title_sort | g quadruplex is critical to epigenetic activation of the lncrna hotair in cancer cells |
| topic | Molecular Structure Epigenetics Cancer Transcriptomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223026366 |
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