Silencing of long noncoding RNA TUG1 inhibits viability and promotes apoptosis of acute myeloid leukemia cells by targeting microRNA-221-3p/KIT axis

2020 ◽  
Vol 76 (3) ◽  
pp. 425-437 ◽  
Author(s):  
Xifeng Zhang ◽  
Likun Yang ◽  
Guixia Xu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Long Noncoding Rna ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
World Health ◽  
Luciferase Reporter ◽  
Who Grade ◽  
Acute Myeloid Leukemia Cells ◽  
Acute Myeloid

OBJECTIVE: Acute myeloid leukemia (AML) is a hematological malignancy. This study was attempted to uncover the effects of long noncoding RNA taurine-upregulated gene1 (TUG1) on the viability and apoptosis of AML cells. METHODS: QRT-PCR was implemented to examine the expression of TUG1, miR-221-3p and KIT in AML. The correlation between TUG1 and clinicopathological features of AML patients was evaluated. The effect of TUG1 on AML cells were studied by RNA interference approach. AML cells were transfected with miR-221-3p mimic and miR-221-3p inhibitor, respectively. Then the viability and apoptosis of AML cells were examined by MTT and flow cytometry assay, respectively. Additionally, dual-luciferase reporter assay was used to confirm the interactions among TUG1, miR-221-3p and KIT. Western blot was applied to analyze protein expression of KIT. RESULTS: The expression of TUG1 and KIT was up-regulated in AML, but miR-221-3p was down-regulated. TUG1 expression had obviously correlation with World Health Organization (WHO) grade in AML patients. The functional experiment stated that TUG1 silencing suppressed the viability and accelerated the apoptosis of AML cells. Moreover, the mechanical experiment demonstrated that TUG1 and KIT were both targeted by miR-221-3p with the complementary binding sites at 3’UTR. Up-regulation of miR-221-3p inhibited the protein expression of KIT. Furthermore, in the feedback experiment, miR-221-3p inhibition or KIT overexpression reversed the repression of tumor behavior induced by TUG1 silencing. CONCLUSIONS: TUG1 silencing retarded viability and promoted apoptosis of AML cells via regulating miR-221-3p/KIT axis, providing a potential therapeutic target for AML.

Long noncoding RNA GAS6 antisense RNA1 silencing attenuates the tumorigenesis of acute myeloid leukemia cells through targeting microRNA-370-3p/Tetraspanin3 axis

2021 ◽  
pp. 1-13
Author(s):  
Weijuan Lei ◽  
Juliar Lin ◽  
Fang Liu ◽  
Nina Chen
Keyword(s):  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Long Noncoding Rna ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
Pediatric Patients ◽  
Migration And Invasion ◽  
Pediatric Aml ◽  
Acute Myeloid

PURPOSE: Acute myeloid leukemia (AML) is a type of hematologic malignancy. This study was attempt to explore the effect of long noncoding RNA GAS6 antisense RNA1 (GAS6-AS1) on pediatric AML and the regulation mechanisms. METHODS: GAS6-AS1, microRNA-370-3p (miR-370-3p), and Tetraspanin3 (TSPAN3) expression in bone marrow (BM) tissues and cells was determined by qRT-PCR. The correlation between GAS6-AS1 and clinicopathological features of pediatric patients with AML was assessed. In vitro, viability and migration and invasion of AML cells were evaluated via MTT and transwell assays, respectively. Interactions among GAS6-AS1, miR-370-3p, and TSPAN3 were revealed by dual-luciferase reporter assays. Western blot was applied to confirm the protein expression of TSPAN3. RESULTS: GAS6-AS1 and TSPAN3 expression was elevated in BM tissues of pediatric patients with AML and AML cells, but miR-370-3p expression was reduced. GAS6-AS1 expression was positively related to French-American-British (FAB) classification in pediatric patients with AML. In vitro, GAS6-AS1 deficiency restrained the viability, migration, and invasion of AML cells. Additionally, GAS6-AS1 mediated miR-370-3p expression indeed and TSPAN3 was identified as a target of miR-370-3p. Furthermore, miR-370-3p overexpression repressed the protein expression of TSPAN3. The feedback experiments demonstrated that miR-370-3p inhibition or TSPAN3 overexpression mitigated the suppressive effect of sh-GAS6-AS1 on the tumorigenesis of AML cells. CONCLUSION: GAS6-AS1 silencing restrained AML cell viability, migration, and invasion by targeting miR-370-3p/TSPAN3 axis, affording a novel therapeutic target for pediatric AML.

C/EBPα-Induced Microrna-30c Directly Targets Notch1 During Granulopoiesis and Is Repressed in Acute Myeloid Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3514-3514
Author(s):  
Christiane Katzerke ◽  
Vikas Madan ◽  
Dennis Gerloff ◽  
Daniela Braeuer-Hartmann ◽  
Jens-Uwe Hartmann ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Protein Expression ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Locked Nucleic Acid ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Granulocytic Differentiation ◽  
Knock Out ◽  
Acute Myeloid

Abstract Abstract 3514 The transcription factor CCAAT Enhancer Binding Protein alpha (C/EBPα) is crucial for normal granulopoiesis and frequently disrupted in acute myeloid leukemia (AML). Mutations in the CEBPA gene are reported for about 10% of all AML. Loss of function of C/EBPα leads to a block of myeloid differentiation. MicroRNAs (miR) inhibiting translation of mRNA into protein were identified as critical players in granulocytic differentiation. We and others have already shown that C/EBPα exerts its effects by regulating miRNAs such as miR-223 and miR-34a. In a global microRNA-array we found miR-30c as a novel most important target of C/EBPα during granulopoiesis. Wild-type C/EBPα-p42 up regulates miR-30c expression, whereas the C/EBPα-p30 mutant, found in AML, does not. Furthermore, miR-30c expression is up regulated by G-CSF during granulocytic differentiation of primary human CD34-positive progenitor cells and down regulated in various subtypes of AML. Among these, miR-30c is significantly down regulated in samples from AML with normal karyotype and CEBPA mutations compared to AML patients with CEBPA wildtype. In mice, miR-30c shows a high expression in GMP and granulocytes. An induced tissue specific knock-out of C/EBPα in mice leads to a significant suppression of miR-30c expression in bone marrow cells. A luciferase reporter assay identifies NOTCH1 as a direct target of miR-30c as evident by its binding to the 3'UTR. Recent studies show that Notch1 blocks protein expression of C/EBPα-p42 by activation of Tribbles homolog 2 (Trib2). On the other hand, Proteins of Notch1 and Trib2 are down regulated by C/EBPα-p42. A block of miR-30c by locked nucleic acid (LNA) oligonucleotides prevents C/EBPα–induced downregulation of Notch1 protein expression, thus, miR-30c is necessary for C/EBPα to block NOTCH1. In this direction, the network leads to a block of granulopoiesis and further to leukemogenesis. Our study indicates that C/EBPα-induced miR-30c inactivates Notch1 during granulopoiesis and is down regulated in AML. This data stress the important role of deregulated miRNA expression in leukemia and may provide novel biomarkers and therapeutic targets in AML. Disclosures: Schnittger: MLL Munich Leukemia Laboratory: Equity Ownership.

Long noncoding RNA MIAT promotes the progression of acute myeloid leukemia by negatively regulating miR-495

2019 ◽  
Vol 87 ◽  
pp. 106265 ◽  
Author(s):  
Gaoyan Wang ◽  
Xuerong Li ◽  
Liang Song ◽  
Hua Pan ◽  
Jian Jiang ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Long Noncoding Rna ◽  
Myeloid Leukemia ◽  
Noncoding Rna ◽  
Acute Myeloid
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