Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells
Summary: In this report, we provide evidence showing diminished expression of the mineral dust-induced gene (mdig), a previously identified oncogenic gene, in human triple negative breast cancer (TNBC). Using a mouse model of orthotopic xenograft of the TNBC MDA-MB-231 cells, we demonstrate that mdi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222013293 |
| _version_ | 1811261159221755904 |
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| author | Chitra Thakur Yiran Qiu Qian Zhang Nicholas J. Carruthers Miaomiao Yu Zhuoyue Bi Yao Fu Priya Wadgaonkar Bandar Almutairy Akimasa Seno Paul M. Stemmer Fei Chen |
| author_facet | Chitra Thakur Yiran Qiu Qian Zhang Nicholas J. Carruthers Miaomiao Yu Zhuoyue Bi Yao Fu Priya Wadgaonkar Bandar Almutairy Akimasa Seno Paul M. Stemmer Fei Chen |
| author_sort | Chitra Thakur |
| collection | DOAJ |
| description | Summary: In this report, we provide evidence showing diminished expression of the mineral dust-induced gene (mdig), a previously identified oncogenic gene, in human triple negative breast cancer (TNBC). Using a mouse model of orthotopic xenograft of the TNBC MDA-MB-231 cells, we demonstrate that mdig promotes the growth of primary tumors but inhibits metastasis of these cells in vivo. Knockout of mdig resulted in an enhancement of H3K36me3 in the genome and upregulation of some X chromosome-linked genes for cell motility, invasion, and metastasis. Silencing MAGED2, one of the most upregulated and H3K36me3-enriched genes resulted from mdig depletion, can partially reverse the invasive migration of the mdig knockout cells. The anti-metastatic and inhibitory role of mdig on H3K36me3 was cross-validated in another cell line, A549 lung cancer cells. Together, our data suggest that mdig is antagonist against H3K36me3 that enforces expression of genes, such as MAGED2, for cell invasion and metastasis. |
| first_indexed | 2024-04-12T18:58:18Z |
| format | Article |
| id | doaj.art-1c2cbcbf074541f6a44b5dbfde9a3421 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-12T18:58:18Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1c2cbcbf074541f6a44b5dbfde9a34212022-12-22T03:20:14ZengElsevieriScience2589-00422022-10-012510105057Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cellsChitra Thakur0Yiran Qiu1Qian Zhang2Nicholas J. Carruthers3Miaomiao Yu4Zhuoyue Bi5Yao Fu6Priya Wadgaonkar7Bandar Almutairy8Akimasa Seno9Paul M. Stemmer10Fei Chen11Stony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USAStony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USAInstitute of Environmental Health Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; Cancer Hospital of China Medical University, 44 Xiaoheyan Road, Dadong District, Shenyang, 110042 Liaoning Province, ChinaStony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USAStony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USADepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; College of Pharmacy, Al-Dawadmi Campus, Shaqra University, P.O. Box 11961, Riyadh, Saudi ArabiaDepartment of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; Faculty of Engineering, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, JapanInstitute of Environmental Health Sciences, School of Medicine, Wayne State University, Detroit, MI 48201, USAStony Brook Cancer Center and Department of Pathology, Renaissance School of Medicine, Stony Brook University, Lauterbur Drive, Stony Brook, NY 11794, USA; Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA; Corresponding authorSummary: In this report, we provide evidence showing diminished expression of the mineral dust-induced gene (mdig), a previously identified oncogenic gene, in human triple negative breast cancer (TNBC). Using a mouse model of orthotopic xenograft of the TNBC MDA-MB-231 cells, we demonstrate that mdig promotes the growth of primary tumors but inhibits metastasis of these cells in vivo. Knockout of mdig resulted in an enhancement of H3K36me3 in the genome and upregulation of some X chromosome-linked genes for cell motility, invasion, and metastasis. Silencing MAGED2, one of the most upregulated and H3K36me3-enriched genes resulted from mdig depletion, can partially reverse the invasive migration of the mdig knockout cells. The anti-metastatic and inhibitory role of mdig on H3K36me3 was cross-validated in another cell line, A549 lung cancer cells. Together, our data suggest that mdig is antagonist against H3K36me3 that enforces expression of genes, such as MAGED2, for cell invasion and metastasis.http://www.sciencedirect.com/science/article/pii/S2589004222013293Molecular biologyMolecular mechanism of gene regulationCancer |
| spellingShingle | Chitra Thakur Yiran Qiu Qian Zhang Nicholas J. Carruthers Miaomiao Yu Zhuoyue Bi Yao Fu Priya Wadgaonkar Bandar Almutairy Akimasa Seno Paul M. Stemmer Fei Chen Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells iScience Molecular biology Molecular mechanism of gene regulation Cancer |
| title | Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells |
| title_full | Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells |
| title_fullStr | Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells |
| title_full_unstemmed | Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells |
| title_short | Deletion of mdig enhances H3K36me3 and metastatic potential of the triple negative breast cancer cells |
| title_sort | deletion of mdig enhances h3k36me3 and metastatic potential of the triple negative breast cancer cells |
| topic | Molecular biology Molecular mechanism of gene regulation Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222013293 |
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