ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling

Kazi, Julhash U.; Rupar, Kaja; Marhäll, Alissa; Moharram, Sausan A.; Khanum, Fatima; Shah, Kinjal; Gazi, Mohiuddin; Nagaraj, Sachin Raj M.; Sun, Jianmin; Chougule, Rohit A.

doi:10.18632/oncotarget.14577

Cited by 14 publications

(11 citation statements)

References 34 publications

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“…In migrating cells, PEAK1 is associated with the actin cytoskeleton and focal adhesion and involved in cancer progression [32]. The non-receptor tyrosine-protein kinase ABL2 plays critical roles in inhibiting the proliferation, migration and invasion of cancer cells [33,34]. WWC1, which could restrict cell proliferation and increase cell apoptosis, is considered an important tumor suppressor gene [35,36].…”

Section: Discussionmentioning

confidence: 99%

Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

Zhang²,

Niu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: CD133+CD44+ cancer stem cells previously isolated from laryngeal squamous cell carcinoma (LSCC) cell lines showed strong malignancy and tumorigenicity. However, the molecular mechanism underlying the enhanced malignancy remained unclear. Methods: Cell proliferation assay, spheroid-formation experiment, RNA sequencing (RNA-seq), miRNA-seq, bioinformatic analysis, quantitative real-time PCR, migration assay, invasion assay, and luciferase reporter assay were used to identify differentially expressed mRNAs, lncRNAs, circRNAs and miRNAs, construct transcription regulatory network, and investigate functional roles and mechanism of circRNA in CD133+CD44+ laryngeal cancer stem cells. Results: Differentially expressed genes in TDP cells were mainly enriched in the biological processes of cell differentiation, regulation of autophagy, negative regulation of cell death, regulation of cell growth, response to hypoxia, telomere maintenance, cellular response to gamma radiation, and regulation of apoptotic signaling, which are closely related to the malignant features of tumor cells. We constructed the regulatory network of differentially expressed circRNAs, miRNAs and mRNAs. qPCR findings for the expression of key genes in the network were consistent with the sequencing data. Moreover, our data revealed that circRNA hg19_circ_0005033 promotes proliferation, migration, invasion, and chemotherapy resistance of laryngeal cancer stem cells. Conclusions: This study provides potential biomarkers and targets for LSCC diagnosis and therapy, and provide important evidences for the heterogeneity of LSCC cells at the transcription level.

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Section: Discussionmentioning

confidence: 99%

Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

Zhang²,

Niu³

et al. 2018

Cell Physiol Biochem

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“…ABL2 was annotated in the Ras signalling pathway. Some researchers have identified ABL2 as the target of many regulators to facilitate the proliferation process . Here, we proposed that hsa_circ_0006371 and hsa_circ_0004872 could sponge hsa‐miR‐424‐5p to up‐regulate ABL2 to be involved in the proliferation of HASMCs via the Ras signalling pathway.…”

Section: Discussionmentioning

confidence: 97%

Screening and functional prediction of differentially expressed circRNAs in proliferative human aortic smooth muscle cells

Chen

Lin

et al. 2020

J Cellular Molecular Medi

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| INTRODUC TI ONCardiovascular diseases (CVD), including vascular remodelling diseases, are the leading cause of mortality among humans throughout the world. Abnormal proliferation of vascular smooth muscle cells (VSMCs) is a common feature of many vascular remodelling diseases, including atherosclerosis, 1 hypertension 2 and vascular aneurysms. 3 The regulation of VSMC proliferation has been considered a key event due to its major implications for the prevention of pathological vascular conditions. 4 Non-coding RNAs (ncRNAs) form the dominant product of eukaryotic transcription, comprising over 73% of the human genome. 5 Circular RNAs (circRNAs) are a special novel type of endogenous ncRNAs, forming covalently closed-loop structures without 5′ caps Abstract Vascular smooth muscle cell (VSMC) proliferation is the pathological base of vascular remodelling diseases. Circular RNAs (circRNAs) are important regulators involved in various biological processes. However, the function of circRNAs in VSMC proliferation regulation remains largely unknown. This study was conducted to identify the key differentially expressed circRNAs (DEcircRNAs) and predict their functions in human aortic smooth muscle cell (HASMC) proliferation. To achieve this, DEcircRNAs between proliferative and quiescent HASMCs were detected using a microarray, followed by quantitative real-time RT-PCR validation. A DEcircRNA-miRNA-DEmRNA network was constructed, and functional annotation was performed using Gene Ontology (GO) and KEGG pathway analysis. The function of hsa_circ_0002579 in HASMC proliferation was analysed by Western blot. The functional annotation of the DEcircRNA-miRNA-DEmRNA network indicated that the four DEcircRNAs might play roles in the TGF-β receptor signalling pathway, Ras signalling pathway, AMPK signalling pathway and Wnt signalling pathway. Twenty-seven DEcircRNAs with coding potential were screened. Hsa_circ_0002579 might be a pro-proliferation factor of HASMC. Overall, our study identified the key DEcircRNAs between proliferative and quiescent HASMCs, which might provide new important clues for exploring the functions of circRNAs in vascular remodelling diseases. K E Y W O R D S circular RNAs, coding potential, HASMCs, microRNA sponge, proliferation | 4763 CHEN Et al.

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“…One possible reason is that ABL2 affects not only Flt3 (fms-like tyrosine kinase 3 ligand) signaling but also AKT (also known as protein kinase B) signaling. 53 All these factors have been shown to be involved in the regulation of IL- 10 signaling. 54,55 In fact, T cells lacking ABL kinases exhibit reduced proliferation and production of IL-2 and IFN-c but display similar levels of IL-4 in response to T cell receptor stimulation.…”

Section: Discussionmentioning

confidence: 99%

Replication of Genome-Wide Association Analysis Identifies New Susceptibility Loci at Long Noncoding RNA Regions for Vogt-Koyanagi-Harada Disease

Deng

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Citation: Qi J, Du L, Deng J, et al. Replication of genome-wide association analysis identifies new susceptibility loci at long noncoding RNA regions for Vogt-Koyanagi-Harada disease. Invest Ophthalmol Vis Sci. 2019;60:4820-4829. https://doi.org/ 10.1167/iovs.19-27708PURPOSE. This study was aimed at investigating the association of long noncoding RNA (lncRNA)-related single nucleotide polymorphisms (SNPs) with Vogt-Koyanagi-Harada (VKH) disease. METHODS.LncRNA-related SNPs were selected by multi-omics analysis. Genotyping, expression of lncRNA and mRNA, cell proliferation, and cytokine production were tested by MassARRAY System, real-time PCR, CCK8, and ELISA. RESULTS.A significant association with VKH was found for lnc-TOR3A-1:1/rs3829794, which is located in a non-HLA region (CC genotype: Bonferroni corrected P values [P C ] ¼ 2.98 3 10 À8 , odds ratio [OR] ¼ 0.62; TT genotype: P C ¼ 1.64 3 10 À8 , OR ¼ 1.57; C allele: P C ¼ 1.39 3 10 À12 , OR ¼ 0.71). Additionally, an association was found for four lncRNA SNPs located in the HLA region. Functional experiments in rs3829794 genotyped individuals showed decreased ABL2 (ABL proto-oncogene 2, nonreceptor tyrosine kinase) expression, decreased proliferation of anti-CD3 plus anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs), and an increased production of IL-10 in CC carriers compared to TT carriers (P ¼ 0.0073, P ¼ 0.0011, and P ¼ 0.002, respectively). CONCLUSIONS.Our study identified five new loci associated with VKH susceptibility and identified a functional variant (lnc-TOR3A-1:1/rs3829794) that confers risk for VKH, which is possibly mediated by modulating gene expression, proliferation of lymphocytes, and regulation of anti-inflammatory cytokine production.

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ABL2 suppresses FLT3-ITD-induced cell proliferation through negative regulation of AKT signaling

Cited by 14 publications

References 34 publications

Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

Whole-Transcriptome Analysis of CD133+CD144+ Cancer Stem Cells Derived from Human Laryngeal Squamous Cell Carcinoma Cells

Screening and functional prediction of differentially expressed circRNAs in proliferative human aortic smooth muscle cells

Replication of Genome-Wide Association Analysis Identifies New Susceptibility Loci at Long Noncoding RNA Regions for Vogt-Koyanagi-Harada Disease

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