Cytoplasmic DROSHA and non-canonical mechanisms of MiR-155 biogenesis in FLT3-ITD acute myeloid leukemia.
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
10
11
2020
accepted:
26
01
2021
revised:
07
01
2021
pubmed:
17
2
2021
medline:
1
9
2021
entrez:
16
2
2021
Statut:
ppublish
Résumé
We report here on a novel pro-leukemogenic role of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) that interferes with microRNAs (miRNAs) biogenesis in acute myeloid leukemia (AML) blasts. We showed that FLT3-ITD interferes with the canonical biogenesis of intron-hosted miRNAs such as miR-126, by phosphorylating SPRED1 protein and inhibiting the "gatekeeper" Exportin 5 (XPO5)/RAN-GTP complex that regulates the nucleus-to-cytoplasm transport of pre-miRNAs for completion of maturation into mature miRNAs. Of note, despite the blockage of "canonical" miRNA biogenesis, miR-155 remains upregulated in FLT3-ITD+ AML blasts, suggesting activation of alternative mechanisms of miRNA biogenesis that circumvent the XPO5/RAN-GTP blockage. MiR-155, a BIC-155 long noncoding (lnc) RNA-hosted oncogenic miRNA, has previously been implicated in FLT3-ITD+ AML blast hyperproliferation. We showed that FLT3-ITD upregulates miR-155 by inhibiting DDX3X, a protein implicated in the splicing of lncRNAs, via p-AKT. Inhibition of DDX3X increases unspliced BIC-155 that is then shuttled by NXF1 from the nucleus to the cytoplasm, where it is processed into mature miR-155 by cytoplasmic DROSHA, thereby bypassing the XPO5/RAN-GTP blockage via "non-canonical" mechanisms of miRNA biogenesis.
Identifiants
pubmed: 33589748
doi: 10.1038/s41375-021-01166-9
pii: 10.1038/s41375-021-01166-9
pmc: PMC8973317
mid: NIHMS1666866
doi:
Substances chimiques
MIRN155 microRNA, human
0
MicroRNAs
0
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
DROSHA protein, human
EC 3.1.26.3
Ribonuclease III
EC 3.1.26.3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2285-2298Subventions
Organisme : NCI NIH HHS
ID : R01 CA205247
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA250046
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141379
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA248475
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA201184
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
Références
Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15:509–24.
doi: 10.1038/nrm3838
pubmed: 25027649
Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, et al. Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci USA. 2008;105:3945–50.
pubmed: 18308931
pmcid: 2268779
doi: 10.1073/pnas.0800135105
Liao Q, Wang B, Li X, Jiang G. miRNAs in acute myeloid leukemia. Oncotarget. 2017;8:3666–82.
pubmed: 27705921
doi: 10.18632/oncotarget.12343
Marcucci G, Radmacher MD, Maharry K, Mrozek K, Ruppert AS, Paschka P, et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1919–28.
pubmed: 18450603
doi: 10.1056/NEJMoa074256
Wallace JA, O’Connell RM. MicroRNAs and acute myeloid leukemia: therapeutic implications and emerging concepts. Blood. 2017;130:1290–301.
pubmed: 28751524
pmcid: 5600138
doi: 10.1182/blood-2016-10-697698
Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33:299–312.
pubmed: 30651634
pmcid: 6365380
doi: 10.1038/s41375-018-0357-9
Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377:454–64.
pubmed: 28644114
pmcid: 5754190
doi: 10.1056/NEJMoa1614359
Marcucci G, Maharry KS, Metzeler KH, Volinia S, Wu YZ, Mrozek K, et al. Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients. J Clin Oncol. 2013;31:2086–93.
pubmed: 23650424
pmcid: 3731981
doi: 10.1200/JCO.2012.45.6228
Gerloff D, Grundler R, Wurm AA, Brauer-Hartmann D, Katzerke C, Hartmann JU, et al. NF-kappaB/STAT5/miR-155 network targets PU.1 in FLT3-ITD-driven acute myeloid leukemia. Leukemia. 2015;29:535–47.
pubmed: 25092144
doi: 10.1038/leu.2014.231
Wallace JA, Kagele DA, Eiring AM, Kim CN, Hu R, Runtsch MC, et al. miR-155 promotes FLT3-ITD-induced myeloproliferative disease through inhibition of the interferon response. Blood. 2017;129:3074–86.
pubmed: 28432220
pmcid: 5465836
doi: 10.1182/blood-2016-09-740209
Narayan N, Bracken CP, Ekert PG. MicroRNA-155 expression and function in AML: an evolving paradigm. Exp Hematol. 2018;62:1–6.
pubmed: 29601851
doi: 10.1016/j.exphem.2018.03.007
de Leeuw DC, Denkers F, Olthof MC, Rutten AP, Pouwels W, Schuurhuis GJ, et al. Attenuation of microRNA-126 expression that drives CD34+38- stem/progenitor cells in acute myeloid leukemia leads to tumor eradication. Cancer Res. 2014;74:2094–105.
pubmed: 24477595
doi: 10.1158/0008-5472.CAN-13-1733
Dorrance AM, Neviani P, Ferenchak GJ, Huang X, Nicolet D, Maharry KS, et al. Targeting leukemia stem cells in vivo with antagomiR-126 nanoparticles in acute myeloid leukemia. Leukemia. 2015;29:2143–53.
pubmed: 26055302
pmcid: 4633325
doi: 10.1038/leu.2015.139
Lechman ER, Gentner B, van Galen P, Giustacchini A, Saini M, Boccalatte FE, et al. Attenuation of miR-126 activity expands HSC in vivo without exhaustion. Cell Stem Cell. 2012;11:799–811.
pubmed: 23142521
pmcid: 3517970
doi: 10.1016/j.stem.2012.09.001
Lechman ER, Gentner B, Ng SW, Schoof EM, van Galen P, Kennedy JA, et al. miR-126 regulates distinct self-renewal outcomes in normal and malignant hematopoietic stem cells. Cancer Cell. 2016;29:214–28.
pubmed: 26832662
pmcid: 4749543
doi: 10.1016/j.ccell.2015.12.011
Zhang B, Nguyen LXT, Li L, Zhao D, Kumar B, Wu H, et al. Bone marrow niche trafficking of miR-126 controls the self-renewal of leukemia stem cells in chronic myelogenous leukemia. Nat Med. 2018;24:450–62.
pubmed: 29505034
pmcid: 5965294
doi: 10.1038/nm.4499
Zorko NA, Bernot KM, Whitman SP, Siebenaler RF, Ahmed EH, Marcucci GG, et al. Mll partial tandem duplication and Flt3 internal tandem duplication in a double knock-in mouse recapitulates features of counterpart human acute myeloid leukemias. Blood. 2012;120:1130–6.
pubmed: 22674806
pmcid: 3412333
doi: 10.1182/blood-2012-03-415067
Cancer Genome Atlas Research N, Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368:2059–74.
doi: 10.1056/NEJMoa1301689
Zarrinkar PP, Gunawardane RN, Cramer MD, Gardner MF, Brigham D, Belli B, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. 2009;114:2984–92.
pubmed: 19654408
pmcid: 2756206
doi: 10.1182/blood-2009-05-222034
Roberts TC. The microRNA biology of the mammalian nucleus. Mol Ther Nucleic Acids. 2014;3:e188.
pubmed: 25137140
pmcid: 4221600
doi: 10.1038/mtna.2014.40
Bohnsack MT, Czaplinski K, Gorlich D. Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. RNA. 2004;10:185–91.
pubmed: 14730017
pmcid: 1370530
doi: 10.1261/rna.5167604
Okamura M, Inose H, Masuda S. RNA export through the NPC in eukaryotes. Genes (Basel). 2015;6:124–49.
doi: 10.3390/genes6010124
Wakioka T, Sasaki A, Kato R, Shouda T, Matsumoto A, Miyoshi K, et al. Spred is a Sprouty-related suppressor of Ras signalling. Nature. 2001;412:647–51.
pubmed: 11493923
doi: 10.1038/35088082
Brems H, Pasmant E, Van Minkelen R, Wimmer K, Upadhyaya M, Legius E, et al. Review and update of SPRED1 mutations causing Legius syndrome. Hum Mutat. 2012;33:1538–46.
pubmed: 22753041
doi: 10.1002/humu.22152
Quintanar-Audelo M, Yusoff P, Sinniah S, Chandramouli S, Guy GR. Sprouty-related Ena/vasodilator-stimulated phosphoprotein homology 1-domain-containing protein (SPRED1), a tyrosine-protein phosphatase non-receptor type 11 (SHP2) substrate in the Ras/extracellular signal-regulated kinase (ERK) pathway. J Biol Chem. 2011;286:23102–12.
pubmed: 21531714
pmcid: 3123077
doi: 10.1074/jbc.M110.212662
Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15:261–71.
pubmed: 18694565
pmcid: 2685763
doi: 10.1016/j.devcel.2008.07.002
Fuhrer S, Ahammer L, Ausserbichler A, Scheffzek K, Dunzendorfer-Matt T, Tollinger M. NMR resonance assignments of the EVH1 domain of neurofibromin’s recruitment factor Spred1. Biomol NMR Assign. 2017;11:305–8.
pubmed: 28831766
pmcid: 5594049
doi: 10.1007/s12104-017-9768-1
Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. 2004;303:95–8.
pubmed: 14631048
doi: 10.1126/science.1090599
Elton TS, Selemon H, Elton SM, Parinandi NL. Regulation of the MIR155 host gene in physiological and pathological processes. Gene. 2013;532:1–12.
pubmed: 23246696
doi: 10.1016/j.gene.2012.12.009
Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, et al. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci USA. 2005;102:3627–32.
pubmed: 15738415
pmcid: 552785
doi: 10.1073/pnas.0500613102
Gatto G, Rossi A, Rossi D, Kroening S, Bonatti S, Mallardo M. Epstein-Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-kappaB pathway. Nucleic Acids Res. 2008;36:6608–19.
pubmed: 18940871
pmcid: 2582607
doi: 10.1093/nar/gkn666
Rai D, Karanti S, Jung I, Dahia PL, Aguiar RC. Coordinated expression of microRNA-155 and predicted target genes in diffuse large B-cell lymphoma. Cancer Genet Cytogenet. 2008;181:8–15.
pubmed: 18262046
pmcid: 2276854
doi: 10.1016/j.cancergencyto.2007.10.008
Tam W. Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA. Gene. 2001;274:157–67.
pubmed: 11675008
doi: 10.1016/S0378-1119(01)00612-6
Lambert MP, Terrone S, Giraud G, Benoit-Pilven C, Cluet D, Combaret V, et al. The RNA helicase DDX17 controls the transcriptional activity of REST and the expression of proneural microRNAs in neuronal differentiation. Nucleic Acids Res. 2018;46:7686–700.
pubmed: 29931089
pmcid: 6125624
doi: 10.1093/nar/gky545
Zhao L, Mao Y, Zhao Y, He Y. DDX3X promotes the biogenesis of a subset of miRNAs and the potential roles they played in cancer development. Sci Rep. 2016;6:32739.
pubmed: 27586307
pmcid: 5009351
doi: 10.1038/srep32739
Lossner C, Meier J, Warnken U, Rogers MA, Lichter P, Pscherer A, et al. Quantitative proteomics identify novel miR-155 target proteins. PLoS ONE. 2011;6:e22146.
pubmed: 21799781
pmcid: 3143118
doi: 10.1371/journal.pone.0022146
Dolde C, Bischof J, Gruter S, Montada A, Halekotte J, Peifer C, et al. A CK1 FRET biosensor reveals that DDX3X is an essential activator of CK1epsilon. J Cell Sci. 2018;131:jcs207316.
pubmed: 29222110
pmcid: 5818060
Valentin-Vega YA, Wang YD, Parker M, Patmore DM, Kanagaraj A, Moore J, et al. Cancer-associated DDX3X mutations drive stress granule assembly and impair global translation. Sci Rep. 2016;6:25996.
pubmed: 27180681
pmcid: 4867597
doi: 10.1038/srep25996
Brandts CH, Sargin B, Rode M, Biermann C, Lindtner B, Schwable J, et al. Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation. Cancer Res. 2005;65:9643–50.
pubmed: 16266983
doi: 10.1158/0008-5472.CAN-05-0422
Dardenne E, Polay Espinoza M, Fattet L, Germann S, Lambert MP, Neil H, et al. RNA helicases DDX5 and DDX17 dynamically orchestrate transcription, miRNA, and splicing programs in cell differentiation. Cell Rep. 2014;7:1900–13.
pubmed: 24910439
doi: 10.1016/j.celrep.2014.05.010
Fu XD, Ares M Jr. Context-dependent control of alternative splicing by RNA-binding proteins. Nat Rev Genet. 2014;15:689–701.
pubmed: 25112293
pmcid: 4440546
doi: 10.1038/nrg3778
Vu NT, Park MA, Shultz JC, Goehe RW, Hoeferlin LA, Shultz MD, et al. hnRNP U enhances caspase-9 splicing and is modulated by AKT-dependent phosphorylation of hnRNP L. J Biol Chem. 2013;288:8575–84.
pubmed: 23396972
pmcid: 3605676
doi: 10.1074/jbc.M112.443333
Ye J, Beetz N, O’Keeffe S, Tapia JC, Macpherson L, Chen WV, et al. hnRNP U protein is required for normal pre-mRNA splicing and postnatal heart development and function. Proc Natl Acad Sci USA. 2015;112:E3020–29.
pubmed: 26039991
pmcid: 4466706
doi: 10.1073/pnas.1508461112
Gruter P, Tabernero C, von Kobbe C, Schmitt C, Saavedra C, Bachi A, et al. TAP, the human homolog of Mex67p, mediates CTE-dependent RNA export from the nucleus. Mol Cell. 1998;1:649–59.
pubmed: 9660949
doi: 10.1016/S1097-2765(00)80065-9
Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14:1902–10.
pubmed: 15364901
pmcid: 524413
doi: 10.1101/gr.2722704
Bevilacqua V, Gioia U, Di Carlo V, Tortorelli AF, Colombo T, Bozzoni I, et al. Identification of linc-NeD125, a novel long non coding RNA that hosts miR-125b-1 and negatively controls proliferation of human neuroblastoma cells. RNA Biol. 2015;12:1323–37.
pubmed: 26480000
pmcid: 4829289
doi: 10.1080/15476286.2015.1096488
Shaham L, Binder V, Gefen N, Borkhardt A, Izraeli S. MiR-125 in normal and malignant hematopoiesis. Leukemia. 2012;26:2011–8.
pubmed: 22456625
doi: 10.1038/leu.2012.90
Paterson MR, Kriegel AJ. MiR-146a/b: a family with shared seeds and different roots. Physiol Genomics. 2017;49:243–52.
pubmed: 28213571
pmcid: 5407182
doi: 10.1152/physiolgenomics.00133.2016
Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S. Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res. 2007;101:59–68.
pubmed: 17540974
doi: 10.1161/CIRCRESAHA.107.153916
Link S, Grund SE, Diederichs S. Alternative splicing affects the subcellular localization of Drosha. Nucleic Acids Res. 2016;44:5330–43.
pubmed: 27185895
pmcid: 4914122
doi: 10.1093/nar/gkw400
Dai L, Chen K, Youngren B, Kulina J, Yang A, Guo Z, et al. Cytoplasmic Drosha activity generated by alternative splicing. Nucleic Acids Res. 2016;44:10454–66.
pubmed: 27471035
pmcid: 5137420
Li Z, Chen P, Su R, Li Y, Hu C, Wang Y, et al. Overexpression and knockout of miR-126 both promote leukemogenesis. Blood. 2015;126:2005–15.
pubmed: 26361793
pmcid: 4616234
doi: 10.1182/blood-2015-04-639062
Blom N, Sicheritz-Ponten T, Gupta R, Gammeltoft S, Brunak S. Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence. Proteomics. 2004;4:1633–49.
pubmed: 15174133
doi: 10.1002/pmic.200300771
Hanna J, Hossain GS, Kocerha J. The potential for microRNA therapeutics and clinical research. Front Genet. 2019;10:478.
pubmed: 31156715
pmcid: 6532434
doi: 10.3389/fgene.2019.00478