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Table 1 miRNAs in acute myeloid leukemia

From: Role of microRNAs, circRNAs and long noncoding RNAs in acute myeloid leukemia

miRNAs Genetic abnormalities Altered expression Targets Function Reference
miR-9 t(8;21)(q22;q22.1) RUNX1-RUNX1T1; mutated NPM1; biallelic mutations of CEBPA ↑in MLL-rearranged AML RHOH RYBP miR-9 was upregulated by MLL-AF9 and increased MLL-AF9-mediated cell transformation in murine hematopoietic progenitor cells in vitro and in vivo. Mice transplanted with BM progenitors that overexpressed both MLL-AF9 and miR-9 (MLL-AF9+ miR-9) had higher frequency of c-Kit+ blast cells in the BM, spleen, and peripheral blood than MLL-AF9 mice. Moreover, MLL-AF9+ miR-9 leukemic cells had a higher frequency of immature blasts [11]
↓in t(8;21) AML HMGA2 LIN28B Increase proliferation and decrease monocytic differentiation [12]
↓in RUNX1-RUNX1T1(+)AML RUNX1, RUNX1T1, RUNX1-RUNX1T1 RUNX1-RUNX1T1 triggered the heterochromic silencing of miR-9-1, resulting in hypermethylation of the miR-9-1 promoter in t(8; 21) AML. Silencing of miR-9-1 promoted expression of target genes(RUNX1, RUNX1T1, and RUNX1-RUNX1T1), which inhibited differentiation and promoted the proliferation of t(8; 21) AML cell lines [13]
↑3YPERLINK \lline ERG ERG is a direct target of miR-9 which contributed to miR-9/9*-induced differentiation of progenitor cells towards neutrophils [33]
↑3YPERLINK \l "_ENREF_33" \o "Nowek K, 2016 #298" hor><Yeaparients with normal karyotype Hes1 miR-9 negatively regulated Hes1 expression and knockdown of miR-9 suppressed the proliferation of AML cells by the induction of G0 arrest and apoptosis in vitro, decreased circulating leukemic cell counts in peripheral blood and bone marrow, attenuated splenomegaly, and prolonged survival in a xenotransplant mouse model [34]
↓in AE-positive cell lines SIRT1 Knockdown of SIRT1 expression inhibits cell proliferation in AE-positive AML cell lines [87]
↓in EVI1-induced AML FOXO1 FOXO3 Increase proliferation and decrease monocytic differentiation [88]
miR-21 Mutated NPM1; mutated RUNX1 ↑in K562/DNR PTEN Decreased cell sensitivity to daunorubicin [42]
↑in SKM-1 cell PTEN/AKT pathway Downregulation of miR-21 expression inhibits proliferation and induces G1 arrest and apoptosis in SKM-1 cell [89]
miR-22   ↓iR-22LINK \l " CRTC1 FLT3 MYCBP Represses the CREB and MYC pathways [90]
miR-29b PML-RARA; mutated NPM1 ↑in K562 cells DNMT3A DNMT3B DNMT1 Increase DNA methylation and hypermethylation [49]
↓in t(8;21) AML SP1 Upregulate KIT contributing to malignant proliferation [54]
↓in various subtypes of AML AKT2 CCND2 Increase cell growth, leukemic progression in vivo [91]
↓in various subtypes of AML MCL-1 CXXC6 CDK6 Increase cell growth, decrease apoptosis, leukemic progression in vivo [92]
↓in various subtypes of AML SP1 DNMT3A DNMT3B Results in global DNA hypermethylation [93]
↑in NK cells   Damage to NK cells development and function [94]
miR-34a Biallelic mutations of CEBPA ↓in CEBPA mutated AML E2F3 Increase proliferation and decrease differentiation [95]
↓in de novo AML PDL1 Immune dysregulation [96]
↓in CEBPA mutated AML cell lines HMGB1 Inhibit cell apoptosis and increased autophagy [97]
miR-34b   ↓iR-34bINK \l "_ENREF_ CREB Survival signaling pathways [98]
miR-34c-5p   ↓in LSCs RAB27B Increase miR-34c-5p expression induced LSCs senescence ex vivo  
miR-99a Mutated RUNX1; inv(16)(p13.1q22) or t(16;16) (p13.1;q22)    High miR-99a expression could predict worse outcome in AML patients undergoing allo-HCST [80]
↑in initial diagnosis and relapse   Regulate self-renewal, inhibiting differentiation and cell cycle entry [99]
↑in AML-AF9 SMARCA5 HS2ST3 HOXA1 Increase proliferation, colony formation, cell survival, inhibite differentiation [100]
↑in pediatric-onset AML (M1–M5) CTDSPL TRIB2 Increase proliferation, colony formation, cell survival [101]
miR-103   ↑in K562 cells COP1 Increase drug resistance of K562 cells to ADR [102]
miR-125b t(8;21)(q22;q22.1) RUNX1-RUNX1T1; PML-RARA; mutated NPM1 ↑in MDS and AML with t(2;11) (p21;q23)   Inhibit differentiation [103]
↑in AML LIN28A Uncontrolled generation of myeloid cells [104]
  IRF4 Induce myeloid leukemia in mice by inducing immortality, self-renewal, and tumorigenesis in myeloid progenitors [105]
↑in pediatric AML FES PU.1 Block monocytic differentiation of AML in vitro [106]
↑in AML cell lines NF-κB Inhibits human AML cells invasion, proliferation and promotes cells apoptosis [107]
miR-126 t(8;21)(q22;q22.1) RUNX1-RUNX1T1; PML-RARA; mutated NPM1 ↑in t(8;21) and inv(16) AML PLK2 Inhibits cell apoptosis and increase cell viability [108]
↑in LSCs of AML   Increase leukemic growth, and survival of leukemic stem and progenitor cells in vivo [109]
↑in t(8;21) AML ERRFI1 SPRED1 FZD7 Both gain and loss of function of miR-126 promotes leukemogenesis in vivo through targeting distinct gene signaling [110]
↑in LSC of CN-AML   Increase LSC maintenance and self-renewal [111]
↑in LSCs of AML ADAM9, ILK, GOLPH3, CDK3, TOM1 Increase LSC maintenance and self-renewal, quiescence, chemotherapy resistance in vivo [112]
↑in AML cell lines TRAF7 Suppresses apoptosis by downregulating TRAF7, which blocks the c-FLIP pathway [113]
miR-135a   ↓in AML HOXA10 Overexpression of miR-135a inhibits the proliferation and cell cycle and promotes cellular apoptosis [70]
miR-139-5p   ↓iR-139-5p \l "_E EIF4G2 Repressing the translation initiation, specifically inducing the translation of cell cycle inhibitor p27 Kip1 [114]
miR-143   ↑inCD34 + HSPCs ERK5 Increase granulocyte surface marker Ly6G and a more mature morphology toward granulocytes induces apoptosis [115]
miR-144-3p   ↑iR-144-3pnn JU, 2018 #227" e NRF2 Antiapoptotic [116]
miR-146a t(8;21)(q22;q22.1)RUNX1-RUNX1T1; mutated NPM1 ↓in del(5q) MDS TIRAP TRAF6 Inappropriate activation of innate immune signaling in HSPCs and megakaryocytic abnormalities [117]
Knockout in del(5q)MDS/AML   Increase cell survival and proliferation of propagating cells through the TRAF6/p62/NF-κB complex [118]
  IRAK1 miR-146a knockout mice develop myeloid and lymphoid malignancies [119]
   miR-146a deletion leads to myeloproliferation in mice  
Knockout in del(5q) MDS/AML   Co-deletion of TIFAB and miR-146a may cooperate to induce TRAF6 signaling contributing to ineffective hematopoiesis [120]
   miR-146a/Traf6 axis controls autoimmunity and myelopoiesis in mice [121]
↑in elderly AML patients CXCR4 Smad4 Suppress the migration abilities of leukemia cells and promote cell cycle entry in leukemia cells [122]
miR-149-5p   ↑iR-149 FASLG Targeting FASLG led to suppression on cell apoptosis [123]
miR-150 PML-RARA ↓in various subtypes of AML NANOG Increase proliferation, colony, and sphere formation, increase tumor growth in vivo [124]
↓in various subtypes of AML EIF4B, FOXO4, PRKCA, TET3 Increase cell growth and inhibits apoptosis in vitro and in vivo [125]
enriched in Molm-14 exosomes CXCR4 Decrease migration of Ba/F3 cells and the surface expression of CXCR4 [60]
miR-150 miR-155   enriched in exosomes isolated from cultured AML cells c-MYB Hematopoiesis is suppressed by releasing exosomes that contain miR-150/miR155 targeting c-MYB [59]
miR-181a   ↑iR-181aNK \l "_ENREF_59"AML patients KRAS, NRAS, and MAPK1 Targeting the RAS-MAPK-pathway [126]
miR-182-5p PML-RARA; Mutated NPM1; FLT3-ITD ↑in AML cell lines and patients blood sample BCL2L12 BCL2 Promote cell proliferation, and reverse cisplatin (DDP) resistance [40]
↑in APL CEBPα Induce apoptosis [127]
miR-192   ↓in various subtype of AML CCNT2 Increase proliferation and cell cycling, decrease differentiation [128]
miR-193a   ↓iR-AML1/ETO-positive leukemia cells PTEN/PI3K signal pathway AML1/ETO triggers the heterochromatic silencing of microRNA-193a (miR-193a) by binding at AML1-binding sites and recruiting chromatin-remodeling enzymes, which expands the oncogenic activity of AML-ETO, resulting in leukemogenesis [35]
miR-193b Biallelic mutations of CEBPA; mutated NPM1 ↓mutati CCND1,KIT, KRAS, or SOS2 Apoptosis and a G1/S-phase block [74]
miR-196b t(9;11)(p21.3;q23.3) MLLT3-KMT2A; mutated NPM1 ↑in MLL associated AML   Increase proliferation and survival, and decrease differentiation and replating potential [129]
↑in MLL-associated AML HOXA9 Meis1 FAS Inhibit differentiation, promote cell proliferation, and induce leukemic progression in mice [130]
miR-204 Mutated NPM1 ↑in AML cells BIRC6 Lead to AML cell apoptosis [131]
↑in NPMC+ AML HOXA10 Meis1   [132]
miR-221 t(8;21)(q22;q22.1) RUNX1-RUNX1T1; CBFB-MYH1; mutated NPM1 ↑in AML NCL/miR-221/NF-κB/DNMT1 network Involve in DNA hypomethylation [55]
miR-223 t(8;21)(q22;q22.1) RUNX1-RUNX1T1; CBFB-MYH1; PML_RARA; mutated NPM1; mutated RUNX1 ↓in t(8;21) AML   Myeloid differentiation block [133]
↓in various subtypes of AML E2F1 Lead to AML cell apoptosis [134]
↓in AML with adverse prognosis   Impair differentiation [135]
↓in various subtypes of AML FBXW7 Increase cell proliferation and enhance apoptosis [136]
miR-339-5p   ↓in AML cells SOX4 Inhibit cell proliferation of AML cells [137]
miR-345-5p Mutated NPM1 ↓in AML cell lines AKT1/2 Facilitate the proliferation of leukemia cells [138]
miR-370   ↓iR-370 NF1 Activation of the RAS signaling pathway [139]
miR-375   ↓in AML miR-375-HOXB3-CDCA3/ DNMT3B pathway Involve in DNA hypomethylation [56]
miR-7977   ↑in AML cell lines   miR-7977 in extracellular vesicles may be a critical factor that induces failure of normal hematopoiesis via poly(rC) binding protein 1 suppression [61]
miR-26a-5p, miR-101-3p   ↑in exosomes derived from MSCs in AML patients    [58]
miR-23b-5p, miR-339-3p, miR-425-5p   ↓in exosomes derived from MSCs in AML patients    [58]
let-7a, miR-99b, miR-146a, miR-150, miR-155, miR-191, miR -1246   Enriched in exosomes from NSG mice serum    [57]
Let-7c   ↓in AML patients with t(8;21) and inv(16) PBX2 Promotes granulocytic differentiation [140]
  1. Abbreviations: HSPC hematopoietic stem and progenitor cell, LSC leukemia stem cells, MSCs bone marrow mesenchymal stromal cells, NSG NOD/SCID/IL-2rγnull, allo-HSCT allogeneic hematopoietic stem cell transplantation, PB peripheral blood, BM bone marrow