STAT6 phosphorylation upregulates microRNA‑155 expression and subsequently enhances the pathogenesis of chronic lymphocytic leukemia

Chen, Na; Li, Feng; Lu, Kang; Li, Peipei; Lv, Xiao; Wang, Xin

doi:10.3892/ol.2019.10294

Cited by 8 publications

(7 citation statements)

References 28 publications

(33 reference statements)

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“…Furthermore, miR-144-5p, another isoform of miR-144, directly targets Sdc3 in renal cell carcinoma (Rcc) to inhibit the cancer cell growth (31). Additionally, the study by chen et al demonstrated that the low expression of miR-144-3p contributes to the prediction in lung cancer patients (32). These previous studies support the important roles of miR-144-3p in different types of cancer.…”

Section: Discussionmentioning

confidence: 77%

miR‑144‑3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2

Liao

2020

Int J Mol Med

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Accumulating evidence demonstrates that microRNAs (miRNAs or miRs) play important roles in the development and progression of human malignancies, including oral squamous cell carcinoma (OScc); however, the unique roles of miRNAs are not yet fully understood in OScc. The present study aimed to identify novel miRNAs associated with OScc and to elucidate their functions. Based on a microarray analysis, miR-144-3p was found to be one of the most significantly downregulated miRNAs in OSCC tissues. Its low expression was closely associated with tumor size, differentiation and lymph node metastasis. Functionally, miR-144-3p overexpression suppressed proliferation, promoted apoptosis, and suppressed the invasion and migration of OScc cells. In addition, enhancer of zeste homolog 2 (EZH2), a well-known oncogene, was proven to be a direct target of miR-144-3p, and its protein expression was negatively regulated by miR-144-3p. Moreover, EZH2 expression was increased, and inversely correlated with the miR-144-3p level in OScc tissues. Notably, EZH2 knockdown inhibited cell proliferation, promoted cell apoptosis, and suppressed the invasion and migration of OScc cells, whereas EZH2 overexpression partially reversed the anticancer effects mediated by miR-144-3p overexpression. On the whole, the findings of the present study suggest that miR-144-3p functions as a tumor suppressor by targeting the EZH2 oncogene, and may thus be considered as a potential diagnostic and therapeutic target for OScc.

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Section: Discussionmentioning

confidence: 77%

miR‑144‑3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2

Liao

2020

Int J Mol Med

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“…Many miRs are considered as factors influencing CLL risk and prognosis, among others miR-155-5p. The expression of this miR is upregulated and associated with higher disease risk and poorer prognosis [ 29 – 31 ]. The influence of miRs' epigenetic regulation of BTLA protein expression is the subject of our ongoing study.…”

Section: Discussionmentioning

confidence: 99%

Abnormal Expression of BTLA and CTLA-4 Immune Checkpoint Molecules in Chronic Lymphocytic Leukemia Patients

Karabon

Partyka

Ciszak

et al. 2020

Journal of Immunology Research

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Chronic lymphocytic leukemia (CLL) is characterized by the peripheral accumulation of neoplastic B cells and is frequently complicated by the systemic immunosuppression associated with an impairment in B and T lymphocyte activation. We hypothesized that the expression of immune checkpoint suppressors B and T lymphocyte attenuator (BTLA) and cytotoxic T lymphocyte antigen (CTLA-4) is disturbed in both lymphocyte subpopulations in CLL. The expression of CTLA-4 and BTLA mRNA was determined by real-time PCR, while CTLA-4 protein expression (surface or intracellular) was estimated in BTLA+ lymphocytes by flow cytometry. In CLL patients, we observed a higher gene transcript level of BTLA and CTLA-4 than in healthy individuals in both freshly isolated and PMA stimulated B and T cells. Remarkably, lower amounts of both inhibitory proteins were found in peripheral blood (PB) CLL B cells, whereas normal BTLA and elevated CTLA-4 were found in T cells. Consistently, there was a prevalence of CTLA-4+ cells within circulating BTLA+ T cells cells of patients confronting PB healthy cells. After in vitro stimulation, the only change found in CLL patients was a decrease in BTLA expression in B and T lymphocytes. In contrast, healthy lymphocytes responded more vigorously as regards the BTLA and CTLA expression with substantially higher frequency of CD69+ cells under the stimulating condition compared to corresponding cells from the CLL group. Our results indicate that CLL development is associated with the affected expression of BTLA and CTLA-4 checkpoint receptors in PB and its impaired expression might be associated with lowering of the threshold for B cell activation and proliferation, while upregulated CTLA-4 expression in CLL peripheral BTLA+ T cells may contribute to suppressed T cell effector functions. This hypothesis needs to be validated in future studies, which would allow us to explain how the increased or decreased expression of these molecules affects the cell function.

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“…Sự phosphoryl hóa STAT5 làm khởi phát bệnh đồng thời duy trì sự sống của tế bào ung thư (Hantschel et al, 2012). Hoạt hóa tín hiệu phân tử STAT6 cũng làm tăng nguy cơ mắc bệnh ung thư máu (Chen et al, 2019b). Ngoài ra, các nghiên cứu về phân tử tín hiệu nuclear factor κB (NF-κB) cũng rất được chú ý. Khi tế bào ở trạng thái nghỉ, NF-κB tương tác với các protein ức chế là IκB trong đó có IκB-α.…”

Section: Tóm Tắtunclassified

“…Tương tự với các nghiên cứu về ung thư trước đó (Meissl et al, 2017;Chen et al, 2019b), chúng tôi cũng chỉ ra rằng, mức độ biểu hiện của STAT1 và STAT6 ở bệnh nhân CML cao hơn so với người khỏe mạnh. STAT6 biểu hiện tăng cao trong các dòng tế bào có nguồn gốc từ những u lympho Hodgkin.…”

Section: Biểu Hiện Một Số Gen Tín Hiệu Trên Bệnh Nhân CMLunclassified

Expression of genes involved in immune regulation in chronic myeloid leukemia

Giang¹,

Huyền²,

Xuân³

2021

Vietnam J. Biotechnol.

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Chronic myeloid leukemia (CML) is a blood cancer involved in abnormal proliferation of myeloid cells at all stages of differentiation. Translocation of regions of the BCR and ABL genes, leading to the fusion gene BCR-ABL, which forms the Philadelphia (Ph) chromosome, is the cause of more than 90% of CML. The BCR-ABL protein shows abnormal tyrosine kinase activity, leading to changes in proliferation signals including signal transducer and activator of transcriptions (STATs) and nuclear factor kappa-light-chain-enhancer of activated B (NF-κB) and resulting in uncontrolled proliferation of myeloid cells. CTLA-4, PD-1 and LAG3 genes are known as immunosuppressive receptors playing important roles in controlling immune response by inhibiting activity of T helper cells. Klotho gene has anti-aging, anti-inflammatory and anti-cancer functions. STAT signaling pathway genes regulate cancer cell functions by their phosphorylation and IκB-α gene by degradation of its expression. In this study, we conducted experiments to determine mRNA expression of these genes on immune cells in CML patients by using realtime-PCR. Results showed a marked increase in the expression of STAT-1 and STAT-6 signaling genes and a decreased LAG3 expression in CML patients as compared with healthy controls. In addition, other gene expressions such as CTLA4, PD1, klotho, IκB-α, STAT3 and STAT5 were unaltered in CML cells. The abnormal increased expression of STAT1 and STAT6 genes indicated an important role of these signaling genes in regulating activity of immune cells, leading to pathogenesis and development of CML disease. The evidence suggested that STAT-1 and STAT-6 genes could be important and potential markers in early prognosis of CML.

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STAT6 phosphorylation upregulates microRNA‑155 expression and subsequently enhances the pathogenesis of chronic lymphocytic leukemia

Cited by 8 publications

References 28 publications

miR‑144‑3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2

miR‑144‑3p inhibits tumor cell growth and invasion in oral squamous cell carcinoma through the downregulation of the oncogenic gene, EZH2

Abnormal Expression of BTLA and CTLA-4 Immune Checkpoint Molecules in Chronic Lymphocytic Leukemia Patients

Expression of genes involved in immune regulation in chronic myeloid leukemia

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