دورية أكاديمية
RGS1 and CREB5 are direct and common transcriptional targets of ZNF384-fusion proteins.
العنوان: | RGS1 and CREB5 are direct and common transcriptional targets of ZNF384-fusion proteins. |
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المؤلفون: | Yamada C; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan., Okada K; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan., Odaira K; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan., Tokoro M; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan., Iwamoto E; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan., Sanada M; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan., Noura M; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan., Okamoto S; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan., Yasuda T; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan., Tsuzuki S; Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Japan., Kiyoi H; Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan., Hayakawa F; Division of Cellular and Genetic Sciences, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan. |
المصدر: | Cancer medicine [Cancer Med] 2024 Jul; Vol. 13 (14), pp. e7471. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012- |
مواضيع طبية MeSH: | Cyclic AMP Response Element-Binding Protein*/metabolism , Cyclic AMP Response Element-Binding Protein*/genetics , Oncogene Proteins, Fusion*/genetics , Oncogene Proteins, Fusion*/metabolism , RGS Proteins*/genetics , RGS Proteins*/metabolism, Humans ; Cell Line, Tumor ; Chemokine CXCL12/genetics ; Chemokine CXCL12/metabolism ; Gene Expression Regulation, Leukemic ; Receptors, CXCR4/genetics ; Receptors, CXCR4/metabolism ; Trans-Activators |
مستخلص: | Background: ZNF384-fusion (Z-fusion) genes were recently identified in B-cell acute lymphoblastic leukemia (B-ALL) and are frequent in Japanese adult patients. The frequency is about 20% in those with Philadelphia chromosome-negative B-ALL. ZNF384 is a transcription factor and Z-fusion proteins have increased transcriptional activity; however, the detailed mechanisms of leukemogenesis of Z-fusion proteins have yet to be clarified. Methods: We established three transfectants of cell lines expressing different types of Z-fusion proteins, and analyzed their gene expression profile (GEP) by RNA-seq. We also analyzed the GEP of clinical ALL samples using our previous RNA-seq data of 323 Japanese ALL patients. We selected upregulated genes in both Z-fusion gene-expressing transfectants and Z-fusion gene-positive ALL samples, and investigated the binding of Z-fusion proteins to regulatory regions of the candidate genes by ChIP-qPCR. Results: We selected six commonly upregulated genes. After the investigation by ChIP-qPCR, we finally identified CREB5 and RGS1 as direct and common target genes. RGS1 is an inhibitor of CXCL12-CXCR4 signaling that is required for the homing of hematopoietic progenitor cells to the bone marrow microenvironment and development of B cells. Consistent with this, Z-fusion gene transfectants showed impaired migration toward CXCL12. Conclusions: We identified CREB5 and RGS1 as direct and common transcriptional targets of Z-fusion proteins. The present results provide novel insight into the aberrant transcriptional regulation by Z-fusion proteins. (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.) |
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معلومات مُعتمدة: | 18H02835 Japan Society for the Promotion of Science; 21 K19505 Japan Society for the Promotion of Science; 22H03102 Japan Society for the Promotion of Science; JP 23ck0106851 Japan Agency for Medical Research and Development; JP19ck0106331 Japan Agency for Medical Research and Development; JP22ck0106607 Japan Agency for Medical Research and Development |
فهرسة مساهمة: | Keywords: ZNF384; RNA‐seq; acute lymphoblastic leukemia; fusion gene; transcriptional target |
المشرفين على المادة: | 0 (Chemokine CXCL12) 0 (CXCL12 protein, human) 0 (CXCR4 protein, human) 0 (Cyclic AMP Response Element-Binding Protein) 0 (Oncogene Proteins, Fusion) 0 (Receptors, CXCR4) 0 (RGS Proteins) 0 (RGS1 protein, human) 0 (Trans-Activators) 0 (ZNF384 protein, human) 0 (CREB5 protein, human) |
تواريخ الأحداث: | Date Created: 20240717 Date Completed: 20240717 Latest Revision: 20240722 |
رمز التحديث: | 20240722 |
مُعرف محوري في PubMed: | PMC11252495 |
DOI: | 10.1002/cam4.7471 |
PMID: | 39015025 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-7634 |
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DOI: | 10.1002/cam4.7471 |