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Cited by 62Acute Myeloid Leukemia ResearchMicroRNA in disease regulationRetinoids in leukemia and cellular processes

RETRACTED: The PU.1-Modulated MicroRNA-22 Is a Regulator of Monocyte/Macrophage Differentiation and Acute Myeloid Leukemia

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Shen, Chao, Chen, Ming-Tai, Zhang, Xin-Hua, Yin, Xiao-Lin, Ning, Hong-Mei, Su, Rui, Lin, Hai-Shuang, Song, Li +5 more·2016·PLOS Genetics
DOI 10.1371/journal.pgen.1006259PMC PMC5019412
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Abstract

MicroRNA-22 (miR-22) is emerging as a critical regulator in organ development and various cancers. However, its role in normal hematopoiesis and leukaemogenesis remains unclear. Here, we detected its increased expression during monocyte/macrophage differentiation of HL-60, THP1 cells and CD34 + hematopoietic stem/progenitor cells, and confirmed that PU.1, a key transcriptional factor for monocyte/macrophage differentiation, is responsible for transcriptional activation of miR-22 during the differentiation. By gain- and loss-of-function experiments, we demonstrated that miR-22 promoted monocyte/macrophage differentiation, and MECOM ( EVI1 ) mRNA is a direct target of miR-22 and MECOM (EVI1) functions as a negative regulator in the differentiation. The miR-22-mediated MECOM degradation increased c-Jun but decreased GATA2 expression, which results in increased interaction between c-Jun and PU.1 via increasing c-Jun levels and relief of MECOM- and GATA2-mediated interference in the interaction, and thus promoting monocyte/macrophage differentiation. We also observed significantly down-regulation of PU.1 and miR-22 as well as significantly up-regulation of MECOM in acute myeloid leukemia (AML) patients. Reintroduction of miR-22 relieved the differentiation blockage and inhibited the growth of bone marrow blasts of AML patients. Our results revealed new function and mechanism of miR-22 in normal hematopoiesis and AML development and demonstrated its potential value in AML diagnosis and therapy.

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  • Expression of miR-22 in HL60 and THP1 cell lines increases upon phorbol myristate acetate (PMA) treatment.

    “Expression of miR-22 in HL60 and THP1 cell lines increases upon phorbol myristate acetate (PMA) treatment [185].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [185]

  • miR-22 expression is upregulated by PU.1, targets MECOM (EVI1), which further increases c-Jun but decreases GATA2 expression.

    “It was demonstrated that miR-22, whose expression is upregulated by PU.1 transcription factor, targets MECOM (EVI1), which further increases c-Jun but decreases GATA2 expression.”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [185]

  • Downregulation of miR-22 may appear in acute myeloid leukemia and block differentiation of bone marrow blasts; restoration of its expression relieves the block.

    “Downregulation of miR-22 may appear in acute myeloid leukemia and block differentiation of bone marrow blasts; restoration of its expression relieves the block.”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [185]

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References 53 · Cited by 62

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  1. [2]Blank U, Karlsson S. (2011) The role of Smad signaling in hematopoiesis and translational hematology. Leukemia 25: 1379– 1388. doi: 10.1038/leu.2011.95 21566654 · DOI
  2. [3]Palma CA, Tonna EJ, Ma DF, Lutherborrow M. (2012) MicroRNA control of myelopoiesis and the differentiation block in Acute Myeloid Leukaemia. J Cell Mol Med. PMC4365878 22225649
  3. [4]Sive JI, Gottgens B. (2014) Transcriptional network control of normal and leukaemic haematopoiesis. Exp Cell Res 329: 255– 264. doi: 10.1016/j.yexcr.2014.06.021 25014893 PMC4261078 · DOI
  4. [5]Pospisil V, Vargova K, Kokavec J, Rybarova J, Savvulidi F, Jonasova A, et al. (2011) Epigenetic silencing of the oncogenic miR-17-92 cluster during PU.1-directed macrophage differentiation. EMBO J 30: 4450– 4464. doi: 10.1038/emboj.2011.317 21897363 PMC3230374 · DOI · Paper page
  5. [6]Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis ML, Nervi C, et al. (2005) A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 123: 819– 831. doi: 10.1016/j.cell.2005.09.023 16325577 · DOI
  6. [7]Johnnidis JB, Harris MH, Wheeler RT, Stehling-Sun S, Lam MH, Kirak O, et al. (2008) Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451: 1125– 1129. doi: 10.1038/nature06607 18278031 · DOI · Paper page
  7. [8]Wang XS, Gong JN, Yu J, Wang F, Zhang XH, Yin XL, et al. (2012) MicroRNA-29a and microRNA-142-3p are regulators of myeloid differentiation and acute myeloid leukemia. Blood 119: 4992– 5004. doi: 10.1182/blood-2011-10-385716 22493297 · DOI
  8. [9]Garzon R, Garofalo M, Martelli MP, Briesewitz R, Wang L, Fernandez-Cymering C, et al. (2008) Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin. Proc Natl Acad Sci U S A 105: 3945– 3950. doi: 10.1073/pnas.0800135105 18308931 PMC2268779 · DOI
  9. [10]Li Z, Lu J, Sun M, Mi S, Zhang H, Luo RT, et al. (2008) Distinct microRNA expression profiles in acute myeloid leukemia with common translocations. Proc Natl Acad Sci U S A 105: 15535– 15540. doi: 10.1073/pnas.0808266105 18832181 PMC2563085 · DOI
  10. [11]Marcucci G, Radmacher MD, Maharry K, Mrozek K, Ruppert AS, Paschka P, et al. (2008) MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med 358: 1919– 1928. doi: 10.1056/NEJMoa074256 18450603 · DOI
  11. [12]Jongen-Lavrencic M, Sun SM, Dijkstra MK, Valk PJ, Lowenberg B. (2008) MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood 111: 5078– 5085. doi: 10.1182/blood-2008-01-133355 18337557 · DOI
  12. [13]Garzon R, Volinia S, Liu CG, Fernandez-Cymering C, Palumbo T, Pichiorri F, et al. (2008) MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 111: 3183– 3189. doi: 10.1182/blood-2007-07-098749 18187662 PMC2265455 · DOI
  13. [14]Gong JN, Yu J, Lin HS, Zhang XH, Yin XL, Xiao Z, et al. (2014) The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia. Cell Death Differ 21: 100– 112. doi: 10.1038/cdd.2013.133 24076586 PMC3857615 · DOI
  14. [15]Su R, Lin HS, Zhang XH, Yin XL, Ning HM, Liu B, et al. (2014) MiR-181 family: regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets. Oncogene 34: 3226– 3239. doi: 10.1038/onc.2014.274 25174404 · DOI
  15. [16]Li HS, Greeley N, Sugimoto N, Liu YJ, Watowich SS. (2012) miR-22 controls Irf8 mRNA abundance and murine dendritic cell development. PLoS One 7: e52341. doi: 10.1371/journal.pone.0052341 23251709 PMC3522651 · DOI
  16. [17]Huang ZP, Chen J, Seok HY, Zhang Z, Kataoka M, Hu X, et al. (2013) MicroRNA-22 regulates cardiac hypertrophy and remodeling in response to stress. Circ Res 112: 1234– 1243. doi: 10.1161/CIRCRESAHA.112.300682 23524588 PMC3720677 · DOI
  17. [18]Gurha P, Abreu-Goodger C, Wang T, Ramirez MO, Drumond AL, van Dongen S, et al. (2012) Targeted deletion of microRNA-22 promotes stress-induced cardiac dilation and contractile dysfunction. Circulation 125: 2751– 2761. doi: 10.1161/CIRCULATIONAHA.111.044354 22570371 PMC3503489 · DOI
  18. [19]Chen B, Tang H, Liu X, Liu P, Yang L, Xie X, et al. (2015) miR-22 as a prognostic factor targets glucose transporter protein type 1 in breast cancer. Cancer Lett 356: 410– 417. doi: 10.1016/j.canlet.2014.09.028 25304371 · DOI
  19. [20]Kong LM, Liao CG, Zhang Y, Xu J, Li Y, Huang W, et al. (2014) A regulatory loop involving miR-22, Sp1, and c-Myc modulates CD147 expression in breast cancer invasion and metastasis. Cancer Res 74: 3764– 3778. doi: 10.1158/0008-5472.CAN-13-3555 24906624 · DOI
  20. [21]Ling B, Wang GX, Long G, Qiu JH, Hu ZL. (2012) Tumor suppressor miR-22 suppresses lung cancer cell progression through post-transcriptional regulation of ErbB3. J Cancer Res Clin Oncol 138: 1355– 1361. doi: 10.1007/s00432-012-1194-2 22484852 PMC11824200 · DOI
  21. [22]Alvarez-Diaz S, Valle N, Ferrer-Mayorga G, Lombardia L, Herrera M, Dominguez O, et al. (2012) MicroRNA-22 is induced by vitamin D and contributes to its antiproliferative, antimigratory and gene regulatory effects in colon cancer cells. Hum Mol Genet 21: 2157– 2165. doi: 10.1093/hmg/dds031 22328083 · DOI
  22. [23]Palacios F, Abreu C, Prieto D, Morande P, Ruiz S, Fernandez-Calero T, et al. (2014) Activation of the PI3K/AKT pathway by microRNA-22 results in CLL B-cell proliferation. Leukemia 29: 115– 125. doi: 10.1038/leu.2014.158 24825182 · DOI
  23. [24]Mucenski ML, Taylor BA, Copeland NG, Jenkins NA. (1988) Chromosomal location of Evi-1, a common site of ecotropic viral integration in AKXD murine myeloid tumors. Oncogene Res 2: 219– 233. 2897103
  24. [25]Yuasa H, Oike Y, Iwama A, Nishikata I, Sugiyama D, Perkins A, et al. (2005) Oncogenic transcription factor Evi1 regulates hematopoietic stem cell proliferation through GATA-2 expression. EMBO J 24: 1976– 1987. doi: 10.1038/sj.emboj.7600679 15889140 PMC1142611 · DOI
  25. [26]Laricchia-Robbio L, Premanand K, Rinaldi CR, Nucifora G. (2009) EVI1 Impairs myelopoiesis by deregulation of PU.1 function. Cancer Res 69: 1633– 1642. doi: 10.1158/0008-5472.CAN-08-2562 19208846 · DOI
  26. [27]Barjesteh VWVD, Erpelinck C, van Putten WL, Valk PJ, van der Poel-van DLS, Hack R, et al. (2003) High EVI1 expression predicts poor survival in acute myeloid leukemia: a study of 319 de novo AML patients. Blood 101: 837– 845. doi: 10.1182/blood-2002-05-1459 12393383 · DOI
  27. [28]Vazquez I, Maicas M, Marcotegui N, Conchillo A, Guruceaga E, Roman-Gomez J, et al. (2010) Silencing of hsa-miR-124 by EVI1 in cell lines and patients with acute myeloid leukemia. Proc Natl Acad Sci U S A 107: E167– E168, E169– E170. doi: 10.1073/pnas.1011540107 20930122 PMC2973895 · DOI
  28. [29]Laricchia-Robbio L, Fazzina R, Li D, Rinaldi CR, Sinha KK, Chakraborty S, et al. (2006) Point mutations in two EVI1 Zn fingers abolish EVI1-GATA1 interaction and allow erythroid differentiation of murine bone marrow cells. Mol Cell Biol 26: 7658– 7666. doi: 10.1128/MCB.00363-06 16954386 PMC1636885 · DOI
  29. [30]Patel JB, Appaiah HN, Burnett RM, Bhat-Nakshatri P, Wang G, Mehta R, et al. (2011) Control of EVI-1 oncogene expression in metastatic breast cancer cells through microRNA miR-22. Oncogene 30: 1290– 1301. doi: 10.1038/onc.2010.510 21057539 · DOI
  30. [32]Kataoka K, Sato T, Yoshimi A, Goyama S, Tsuruta T, Kobayashi H, et al. (2011) Evi1 is essential for hematopoietic stem cell self-renewal, and its expression marks hematopoietic cells with long-term multilineage repopulating activity. J Exp Med 208: 2403– 2416. doi: 10.1084/jem.20110447 22084405 PMC3256960 · DOI
  31. [33]Kustikova OS, Schwarzer A, Stahlhut M, Brugman MH, Neumann T, Yang M, et al. (2013) Activation of Evi1 inhibits cell cycle progression and differentiation of hematopoietic progenitor cells. Leukemia 27: 1127– 1138. doi: 10.1038/leu.2012.355 23212151 · DOI
  32. [34]May G, Soneji S, Tipping AJ, Teles J, McGowan SJ, Wu M, et al. (2013) Dynamic analysis of gene expression and genome-wide transcription factor binding during lineage specification of multipotent progenitors. Cell Stem Cell 13: 754– 768. doi: 10.1016/j.stem.2013.09.003 24120743 PMC3878573 · DOI
  33. [35]Zhang P, Behre G, Pan J, Iwama A, Wara-Aswapati N, Radomska HS, et al. (1999) Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1. Proc Natl Acad Sci U S A 96: 8705– 8710. 10411939 PMC17580
  34. [36]Kurokawa M, Mitani K, Yamagata T, Takahashi T, Izutsu K, Ogawa S, et al. (2000) The evi-1 oncoprotein inhibits c-Jun N-terminal kinase and prevents stress-induced cell death. EMBO J 19: 2958– 2968. doi: 10.1093/emboj/19.12.2958 10856240 PMC203342 · DOI
  35. [38]Groschel S, Lugthart S, Schlenk RF, Valk PJ, Eiwen K, Goudswaard C, et al. (2010) High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. J Clin Oncol 28: 2101– 2107. doi: 10.1200/JCO.2009.26.0646 20308656 · DOI
  36. [40]Scott EW, Simon MC, Anastasi J, Singh H. (1994) Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science 265: 1573– 1577. 8079170
  37. [42]Rosa A, Ballarino M, Sorrentino A, Sthandier O, De Angelis FG, Marchioni M, et al. (2007) The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation. Proc Natl Acad Sci U S A 104: 19849– 19854. doi: 10.1073/pnas.0706963104 18056638 PMC2148386 · DOI · Paper page
  38. [43]Lin J, Huo R, Xiao L, Zhu X, Xie J, Sun S, et al. (2014) A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis. Arthritis Rheumatol 66: 49– 59. doi: 10.1002/art.38142 24449575 · DOI
  39. [44]Tsuchiya N, Izumiya M, Ogata-Kawata H, Okamoto K, Fujiwara Y, Nakai M, et al. (2011) Tumor suppressor miR-22 determines p53-dependent cellular fate through post-transcriptional regulation of p21. Cancer Res 71: 4628– 4639. doi: 10.1158/0008-5472.CAN-10-2475 21565979 PMC7425979 · DOI
  40. [45]Chang TC, Yu D, Lee YS, Wentzel EA, Arking DE, West KM, et al. (2008) Widespread microRNA repression by Myc contributes to tumorigenesis. Nat Genet 40: 43– 50. 18066065 PMC2628762
  41. [46]Xiong J. (2012) Emerging roles of microRNA-22 in human disease and normal physiology. Curr Mol Med 12: 247– 258. 22300138
  42. [48]Groschel S, Schlenk RF, Engelmann J, Rockova V, Teleanu V, Kuhn MW, et al. (2013) Deregulated expression of EVI1 defines a poor prognostic subset of MLL-rearranged acute myeloid leukemias: a study of the German-Austrian Acute Myeloid Leukemia Study Group and the Dutch-Belgian-Swiss HOVON/SAKK Cooperative Group. J Clin Oncol 31: 95– 103. doi: 10.1200/JCO.2011.41.5505 23008312 · DOI
  43. [49]Lugthart S, van Drunen E, van Norden Y, van Hoven A, Erpelinck CA, Valk PJ, et al. (2008) High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood 111: 4329– 4337. doi: 10.1182/blood-2007-10-119230 18272813 · DOI
  44. [50]Song SJ, Ito K, Ala U, Kats L, Webster K, Sun SM, et al. (2013) The oncogenic microRNA miR-22 targets the TET2 tumor suppressor to promote hematopoietic stem cell self-renewal and transformation. Cell Stem Cell 13: 87– 101. doi: 10.1016/j.stem.2013.06.003 23827711 PMC3767186 · DOI
  45. [51]Jiang X, Hu C, Arnovitz S, Bugno J, Yu M, Zuo Z, et al. (2016) miR-22 has a potent anti-tumour role with therapeutic potential in acute myeloid leukaemia. Nat Commun 7: 11452. doi: 10.1038/ncomms11452 27116251 PMC5477496 · DOI
  46. [52]Chakrabarti SK, James JC, Mirmira RG. (2002) Quantitative assessment of gene targeting in vitro and in vivo by the pancreatic transcription factor, Pdx1. Importance of chromatin structure in directing promoter binding. J Biol Chem 277: 13286– 13293. 11825903

Authors
Shen, C., Chen, M.-T., Zhang, X.-H., Yin, X.-L., Ning, H.-M., Su, R., Lin, H.-S., Song, L., Wang, F., Ma, Y.-N., Zhao, H.-L., Yu, J., & Zhang, J.-W.
Affiliations
  • Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
  • 303 Hospital of People's Liberation Army (CN)
Corresponding author
Zhang, Jun-Wu
ORCID
Venue
PLOS Genetics
Publisher
Public Library of Science (PLoS)
Published
2016-09-12
Volume
12
Issue
9
Pages
e1006259
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
DOI
10.1371/journal.pgen.1006259
PMC
PMC5019412
OpenAlex
W2520545617
Cited by
62
References
53
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 11 · 2019: 7 · 2018: 5 · 2017: 7
FWCI
6.03
Type
journal article
Language
en
Status
Retracted
Update notices
retraction (2026-07-09)
Open access
Licence
Locations
  • PLoS Genetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
the National Natural Science Foundation of China (31171311, 30970616, 81070435)
Topics
  • Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Keywords
microRNA-22, PU.1, monocyte-to-macrophage differentiation, acute myeloid leukemia, hematopoiesis, c-Jun, GATA2, transcriptional regulation, microRNA target regulation, retracted article
MeSH terms
MDS1 and EVI1 Complex Locus Protein, Proto-Oncogene Protein Spi-1, Cell Differentiation, DNA-Binding Proteins, Hematopoiesis, Hematopoietic Stem Cells, Humans, Macrophages, Monocytes, Proto-Oncogene Proteins, Proto-Oncogenes, Transcription Factors, Leukemia, Myeloid, Acute, Trans-Activators, Gene Expression Regulation, Neoplastic, HL-60 Cells, MicroRNAs, JNK Mitogen-Activated Protein Kinases, GATA2 Transcription Factor

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