دورية أكاديمية
HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate.
| العنوان: | HUWE1 cooperates with RAS activation to control leukemia cell proliferation and human hematopoietic stem cells differentiation fate. |
|---|---|
| المؤلفون: | Ruckert MT; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.; Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Brouwers-Vos AZ; Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Nagano LFP; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil., Schuringa JJ; Department of Experimental Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Silveira VS; Department of Genetics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. vsilveira@fmrp.usp.br. |
| المصدر: | Cancer gene therapy [Cancer Gene Ther] 2020 Nov; Vol. 27 (10-11), pp. 830-833. Date of Electronic Publication: 2020 Jul 10. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 9432230 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5500 (Electronic) Linking ISSN: 09291903 NLM ISO Abbreviation: Cancer Gene Ther Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2002->: London : Nature Publishing Group Original Publication: Norwalk, CT : Appleton & Lange, c1994- |
| مواضيع طبية MeSH: | Genes, ras/*genetics , Hematopoietic Stem Cells/*metabolism , High-Throughput Nucleotide Sequencing/*methods , Leukemia, Myeloid, Acute/*genetics , Tumor Suppressor Proteins/*metabolism , Ubiquitin-Protein Ligases/*metabolism, Cell Differentiation ; Cell Proliferation ; Humans ; Leukemia, Myeloid, Acute/pathology ; Signal Transduction |
| مستخلص: | Acute myeloid leukemia (AML) is a poor prognosis hematopoietic malignance characterized by abnormal proliferation and differentiation of hematopoietic stem cells (HSCs). Although advances in treatment have greatly improved survival rates in young patients, in the elderly population, ~70% of patients present poor prognosis. A pan-cancer analysis on the TCGA cohort showed that AML has the second higher HUWE1 expression in tumor samples among all cancer types. In addition, pathway enrichment analysis pointed to RAS signaling cascade as one of the most important pathways associated to HUWE1 expression in this particular AML cohort. In silico analysis for biological processes enrichment also revealed that HUWE1 expression is correlated with 13 genes involved in myeloid differentiation. Therefore, to understand the role of HUWE1 in human hematopoietic stem and progenitor cells (HSPC) we constitutively expressed KRAS G12V oncogene concomitantly to HUWE1 knockdown in stromal co-cultures. The results showed that, in the context of KRAS G12V , HUWE1 significantly reduces cell cumulative growth and changes myeloid differentiation profile of HSPCs. Overall, these observations suggest that HUWE1 might contribute to leukemic cell proliferation and impact myeloid differentiation of human HSCs, thus providing new venues for RAS-driven leukemia targeted therapy approach. |
| References: | Khwaja A, Bjorkholm M, Gale RE, Levine RL, Jordan CT, Ehninger G, et al. Acute myeloid leukaemia. Nat Rev Dis Prim. 2016;2:16010. (PMID: 10.1038/nrdp.2016.10) Di Genua C, Norfo R, Rodriguez-Meira A, Wen WX, Drissen R, Booth CAG, et al. Cell-intrinsic depletion of Aml1-ETO-expressing pre-leukemic hematopoietic stem cells by K-Ras activating mutation. Haematologica. 2019;104:2215–24. Lai C, Doucette K, Norsworthy K. Recent drug approvals for acute myeloid leukemia. J Hematol Oncol. 2019;12:100. Meyers J, Yu Y, Kaye JA, Davis KL. Medicare fee-for-service enrollees with primary acute myeloid leukemia: an analysis of treatment patterns, survival, and healthcare resource utilization and costs. Appl Health Econ Health Policy. 2013;11:275–86. (PMID: 10.1007/s40258-013-0032-2) Figueroa ME, Lugthart S, Li Y, Erpelinck-Verschueren C, Deng X, Christos PJ, et al. DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 2010;17:13–27. (PMID: 10.1016/j.ccr.2009.11.020) Abdel-Wahab O, Adli M, LaFave LM, Gao J, Hricik T, Shih AH, et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell 2012;22:180–93. (PMID: 10.1016/j.ccr.2012.06.032) Kao SH, Wu HT, Wu KJ. Ubiquitination by HUWE1 in tumorigenesis and beyond. J Biomed Sci. 2018;25:67. (PMID: 10.1186/s12929-018-0470-0) Qi CF, Zhang R, Sun J, Li Z, Shin DM, Wang H, et al. Homeostatic defects in B cells deficient in the E3 ubiquitin ligase ARF-BP1 are restored by enhanced expression of MYC. Leuk Res. 2013;37:1680–9. (PMID: 10.1016/j.leukres.2013.09.009) Hao Z, Duncan GS, Su YW, Li WY, Silvester J, Hong C, et al. The E3 ubiquitin ligase Mule acts through the ATM-p53 axis to maintain B lymphocyte homeostasis. J Exp Med. 2012;209:173–86. (PMID: 10.1084/jem.20111363) King B, Boccalatte F, Moran-Crusio K, Wolf E, Wang J, Kayembe C, et al. The ubiquitin ligase Huwe1 regulates the maintenance and lymphoid commitment of hematopoietic stem cells. Nat Immunol. 2016;17:1312–21. (PMID: 10.1038/ni.3559) Steelman LS, Pohnert SC, Shelton JG, Franklin RA, Bertrand FE, McCubrey JA. JAK/STAT, Raf/MEK/ERK, PI3K/Akt and BCR-ABL in cell cycle progression and leukemogenesis. Leukemia 2004;18:189–218. (PMID: 10.1038/sj.leu.2403241) Fatrai S, van Gosliga D, Han L, Daenen SM, Vellenga E, Schuringa JJ. KRAS(G12V) enhances proliferation and initiates myelomonocytic differentiation in human stem/progenitor cells via intrinsic and extrinsic pathways. J Biol Chem. 2011;286:6061–70. (PMID: 10.1074/jbc.M110.201848) Mirro J, Kitchingman G, Williams D, Lauzon GJ, Lin CC, Callihan T, et al. Clinical and laboratory characteristics of acute leukemia with the 4;11 translocation. Blood 1986;67:689–97. (PMID: 10.1182/blood.V67.3.689.689) Chen MM, Li J, Mills GB, Liang H. Predicting cancer cell line dependencies from the protein expression data of reverse-phase protein arrays. JCO Clin Cancer Inform. 2020;4:357–66. (PMID: 10.1200/CCI.19.00144) Kavianpour M, Ahmadzadeh A, Shahrabi S, Saki N. Significance of oncogenes and tumor suppressor genes in AML prognosis. Tumour Biol. 2016;37:10041–52. (PMID: 10.1007/s13277-016-5067-1) |
| المشرفين على المادة: | 0 (Tumor Suppressor Proteins) EC 2.3.2.26 (HUWE1 protein, human) EC 2.3.2.27 (Ubiquitin-Protein Ligases) |
| تواريخ الأحداث: | Date Created: 20200711 Date Completed: 20210818 Latest Revision: 20210818 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1038/s41417-020-0198-3 |
| PMID: | 32647137 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1476-5500 |
|---|---|
| DOI: | 10.1038/s41417-020-0198-3 |