Low serum miR‐223 expression predicts poor outcome in patients with acute myeloid leukemia

Abstract

Background Identification of biomarkers for acute myeloid leukemia (AML) is important for treating this malignancy. Recent studies have reported that microRNAs (miRNAs) are stably detectable in the blood/plasma and can be used as biomarkers for various types of cancer including AML. The aim of this study was to analyze miR‐223 level in serum as a potential indicator for AML diagnosis and prognosis prediction. Methods Quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) was used to detect the levels of miR‐223 in the serum samples from 131 patients and 70 healthy individuals. Results The results revealed that serum miR‐223 was underexpressed in AML patients, particularly those in intermediate and unfavorable cytogenetic risk groups. Further analysis revealed that serum miR‐223 could yield a receiver operating characteristic (ROC) area under the curve (AUC) of 0.849 with 83.2% sensitivity and 81.4% specificity. Moreover, a significant increase in serum miR‐223 level was observed in AML subjects after their treatment. Reduced serum miR‐223 level was highly associated with aggressive clinical variables and shorter survival of patients. Furthermore, miR‐223 expression was identified to be an independent prognostic predictor of worse overall survival. Conclusion In conclusion, miR‐223 may be a reliable diagnostic and prognostic biomarker for AML.

MicroRNA‑223 overexpression suppresses protein kinase C ε expression in human leukemia stem cell‑like KG‑1a cells

“…However, few studies have explored the role of miR-223 in AML. Previous studies demonstrated low miR-223 expression in patients with AML, especially in those with a poor prognosis (11,12). Moreover, a marked increase in miR-223 expression was reported in patients with AML after treatment, regardless of whether complete remission was achieved or not (12).…”

microRNA expression in acute myeloid leukaemia: New targets for therapy?

“…[104], [105], [106], [107] miR-142 IDH mutation ASH1I, CTNNB1, HOXA [108], [109] miR-155 FLT3+, M4, M5 PU.1, PI3K-AKT, SHIP1 [110], [40] miR-181 M1, M2, M3, CEBPA mutation CAMKK1, CTDSPL, HMGB1, KRAS, MCL-1, MAPK1, NRAS, PRKCD-P38-C/EBPα [111], [24], [112], [66] miR-196 MLL-AML (HOX), FLT3+, M4, M5 ANXA1, ERG, FAS, HOXA9, MEIS1 [51], [113] miR-199 NPM1, M5 DRAM1, ERK, HIF-1α, HOXA7, HOXB6, KRAS-AKT [114], [115] miR-210 Myelodysplastic syndrome C/EBPα, HIF-1α, SHIP1 [42], [43] miR-223 All FAB subtypes E2F1, FBXW7, TP53 [116], [117], [57], [59] miR-378 AML1-ETO, M2, t(8;21) EPOR, FUS1, GZMB [118], [119] miR-451 C-MYC, MDR1, YWHAZ-AKT [62] miR-486 DS-AML PI3K-AKT, SOCS2-JAK-STAT [120], [50] AHS1l, ASH1-like histone lysine methyltransferase; ANXA1, annexin 1; CCND2, cyclin D2; CCNG1, cyclin G1; CDH1, cadherin 1; CDH7, cadherin 7; CDK3/6, cyclin-dependant kinase 3/6; CDX2, caudal-type homeobox 2; CEBPA, CCAAT enhancer binding protein 4; CTNNB1, catenin beta 1; DRAM1, DNA damage regulated autophagy modulator 1; eIF4G2, eukaryotic translation initiation factor 4 gamma 2; EPOR, erythropoietin receptor; E2F3, E2F transcription factor 3; E2F7, E2F transcription factor 7; ERK, extracellular signal-regulated kinase; ERG, ETS transcription factor ERG; ETS-1, ETS proto-oncogene; FOXO1/3, forkhead box O1/O3; FUS1, tumour suppressor 1 calcium regulator; GZMB, granzyme B; ID2, inhibitor of DNA binding 2; JAG1, jagged 1; KRAS, KRAS proto-oncogene; MAPK1, mitogen-activated protein kinase 1; NFκB, nuclear factor kappa B; NKIRAS2, NFκB inhibitor-interacting Ras-like 2; NRAS, NRAS proto-oncogene; P27, cyclin-dependant kinase inhibitor 1B; PDK1, pyruvate dehydrogenase kinase 1; PU.1, Spi-1 proto-oncogene; SIRT1, Sirtuin 1; SOCS2, suppressor of cytokine signalling 2; STMN1, stathmin 1; TET2, Tet methylcytosine dioxygenase 2; TNFα, tumour necrosis factor alpha; TP53, tumour protein 53; TSPAN3, tetraspanin 3; YWHAZ, protein zeta. as a treatment for polycythaemia vera that is being used in clinical trials [28].…”

“…miR-223 underexpression also leads to overexpression of another of its targets, F-box and WD repeat domain containing 7 protein (FBXW7), which was demonstrated as contributing to proliferation and reduced apoptosis in AML[58]. A recent study determined that low miR-223 was a significant independent indicator of poor OS in AML patients while an elevated expression of miR-223 was more prevalent in patients with CR[59]. miR-451 is involved in the late-stage maturation of erythroid cells and is unique amongst miRNAs.…”

The many facets of miR‐223 in cancer: Oncosuppressor, oncogenic driver, therapeutic target, and biomarker of response

“…In acute myeloid leukemia (AML), a cancer of the myeloid line of blood cells, miR‐223 show the opposite trend, with low levels of miR‐223 correlating with poor prognosis of the patients (Gentner et al, 2015 ; Guopan Yu et al, 2020 ). Pulikkan et al discovered an autoregulatory negative feedback loop linking C/EBPα, miR‐223 and E2F1 normally regulating granulopoiesis and dysregulated in AML (Pulikkan et al, 2010 ).…”

“…Moreover, low serum levels of miR‐223 have been correlated with aggressive clinical variables and shorter survival rates. Interestingly, AML patients display a significant increase in miR‐223 levels after treatment, suggesting a strong reliability of miR‐223 serum levels as diagnostic and prognostic biomarker in acute myeloid leukemia patients (Guopan Yu et al, 2020 ).…”