ZNF545 loss promotes ribosome biogenesis and protein translation to initiate colorectal tumorigenesis in mice
| العنوان: | ZNF545 loss promotes ribosome biogenesis and protein translation to initiate colorectal tumorigenesis in mice |
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| المؤلفون: | Shiyan Wang, Housheng Hansen He, Chuangen Li, Xueji Zhang, Junzhe Huang, Jun Yu, Yanquan Zhang, Hong Wei, Jianning Zhai, Chi Chun Wong, Guoping Wang |
| المصدر: | Oncogene |
| بيانات النشر: | Springer Science and Business Media LLC, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Cancer Research, Carcinogenesis, Azoxymethane, Ribosome biogenesis, Cell Communication, Biology, medicine.disease_cause, Article, Mice, Transcriptional repressor complex, Gene expression, Genetics, medicine, Animals, Humans, Cancer genetics, Molecular Biology, Cell Proliferation, Mice, Knockout, Zinc finger, Nuclear Proteins, Translation (biology), Fibroblasts, Ribosomal RNA, RRNA transcription, digestive system diseases, Cell biology, Mice, Inbred C57BL, RNA, Ribosomal, Protein Biosynthesis, Epigenetics, Colorectal Neoplasms, Ribosomes, Cell Nucleolus |
| الوصف: | Ribosome biogenesis plays a pivotal role in tumorigenesis by supporting robust protein translation. We investigate the functional and molecular mechanism of Zinc finger protein 545 (ZNF545), a transcriptional repressor for ribosomal RNA (rRNA), in colorectal cancer (CRC). ZNF545 was silenced in CRC compared to adjacent normal tissues (P Znf545knockout in mice accelerated CRC inApcMin/+and azoxymethane/dextran sulfate sodium-induced CRC. Mechanistically, we demonstrated that ZNF545 uses its two zinc finger clusters to bind to minimal rDNA promoter, where it assembled transcriptional repressor complex by interacting with KAP1.Znf545deletion in mouse embryonic fibroblasts not only increased rRNA transcription rate and the nucleolar size and number but also altered the nucleolar composition and architecture with an increased number of fibrillar centers surrounded by net-like dense fibrillar components. Consequently,Znf545deletion promoted the gene expression of translation machinery, protein translation, and cell growth. Consistent with its tumor-suppressive role, ZNF545 overexpression in CRC cells induced growth arrest and apoptosis. Finally, administration of rRNA synthesis inhibitor, CX-5461, inhibited CRC development inZnf545Δ/ΔApcMin/+mice. In conclusion, ZNF545 suppresses CRC through repressing rRNA transcription and protein translation. Targeting rRNA biosynthesis in ZNF545-silenced tumors is a potential therapeutic strategy for CRC. |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bad3fee940b5abce876660c962aab956Test https://doi.org/10.1038/s41388-021-01938-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bad3fee940b5abce876660c962aab956 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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