Abnormal repression of SHP-1, SHP-2 and SOCS-1 transcription sustains the activation of the JAK/STAT3 pathway and the progression of the disease in multiple myeloma

Beldi‐Ferchiou, Asma; Skouri, Nour; Ali, Cyrine Ben; Safra, Ines; Abdelkefi, Abderrahman; Ladeb, Saloua; Mrad, Karima; Othman, Tarek Ben; Ahmed, Mélika Ben

doi:10.1371/journal.pone.0174835

Cited by 35 publications

(30 citation statements)

References 51 publications

(44 reference statements)

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“…We performed correlation analysis between PTBP1 expression and bone marrow plasma cell infiltration, as derived from bone marrow biopsies. This significant correlation between bone marrow infiltration and PTBP1 expression raises the possibility that PTBP1 may represent a biomarker that indirectly reflects tumor mass and the level of bone marrow invasion at diagnosis [41]. Similarly, we evaluated BZW2 message levels in 241 bortezomib-treated patients paralleled the myeloma proliferation score, which was scored with the assistance of GPI model constructed by Hose and his associates [42].…”

Section: Discussionmentioning

confidence: 99%

Abnormal PTBP1 Expression Sustains the Disease Progression of Multiple Myeloma

Bai

Chen

2020

Disease Markers

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Multiple myeloma (MM) is a hematopoietic malignancy characterized by heterogeneity, which corresponds to alternative splicing (AS) profiles and disadjust gene expression. Bioinformatics analysis of AS factors possibly related to MM progression identified the polypyrimidine tract binding protein (PTBP1) as candidate. The purpose of this study was to confirm the incidence and prognostic value of PTBP1 in MM patients. Several cohorts of 2971 patients presenting newly diagnosed and relapsed MM were enrolled. Correlations between PTBP1 expression and clinicopathological characteristics, proliferative activity, and response to therapy of myeloma cells were analyzed. Moreover, the effect of PTBP1 on the AS pattern of specific aerobic glycolysis-related genes was explored in MM patients. Clinically, PTBP1 expression was present at all stages; it increased with disease progression and poor prognosis, which was even stronger elevated in patients with high tumor burden and drug resistance. Mechanistically, PTBP1 modulated AS of PKM2 and aerobic glycolysis-related genes in MM patients, which play synergistic or additive effects in clinical outcome. PTBP1 may be a novel marker for prognostic prediction and a promising therapeutic target for the development of anti-MM treatments.

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Section: Discussionmentioning

confidence: 99%

Abnormal PTBP1 Expression Sustains the Disease Progression of Multiple Myeloma

Bai

Chen

2020

Disease Markers

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“…The SHP-1 protein contains two tandem Src homolog (SH2) domains which act as protein phospho-tyrosine binding domains, a catalytic protein tyrosine phosphatase (PTP) domain and a C-terminal tail [ 75 ]. SHP-1 has been reported as a tumor suppressor and a negative regulator of STAT3 in various cancer types [ 66 , 76 , 77 , 78 ]. The HCC cell lines with lower expression of SHP-1 showed higher expression of p-STAT3 Tyr705, and statistical analysis on HCC samples showed expression of SHP-1 had a negative correlation with p-STAT3 Tyr705 [ 21 ].…”

Section: Ptps Involved In Hccmentioning

confidence: 99%

The Roles of Protein Tyrosine Phosphatases in Hepatocellular Carcinoma

Huang

Zhang

et al. 2018

Cancers

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The protein tyrosine phosphatase (PTP) family is involved in multiple cellular functions and plays an important role in various pathological and physiological processes. In many chronic diseases, for example cancer, PTP is a potential therapeutic target for cancer treatment. In the last two decades, dozens of PTP inhibitors which specifically target individual PTP molecules were developed as therapeutic agents. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and is the second most lethal cancer worldwide due to a lack of effective therapies. Recent studies have unveiled both oncogenic and tumor suppressive functions of PTP in HCC. Here, we review the current knowledge on the involvement of PTP in HCC and further discuss the possibility of targeting PTP in HCC.

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“…JAK/STAT is a common signalling pathway shared by many cytokines and growth factors . This notion supports the crucial and complicated role of this pathway in the biology of haematopoietic cells, oncogenesis, and therapy for some blood malignancies . Specifically, the IL‐6R/JAK/STAT3 pathway principally makes contribution to the pathogenesis and multistep transformation process of multiple myeloma, making its therapeutic targeting an attractive strategy for durable remissions in patients with multiple myeloma .…”

Section: Discussionmentioning

confidence: 66%

Role of IL‐9 and IL‐10 in the pathogenesis of chronic spontaneous urticaria through the JAK/STAT signalling pathway

Feng

Zhang

et al. 2020

Cell Biochemistry & Function

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This study investigated the role of interleukin (IL)-9 and IL-10 in the pathogenesis of chronic spontaneous urticaria (CSU). Autologous serum skin test and histamine release test were performed in CSU patients and normal subjects. Kunming mice were used to develop a mouse model for CSU. We induced IL-9 overexpression, IL-10 overexpression, and JAK/STAT pathway inhibition as well as a combination of all three conditions in CSU and control mice. Eosinophils in the skin tissues, inflammatory cytokine expression, and distribution of T lymphocyte subsets in peripheral blood of mice were detected. Expression patterns of IL-9, IL-10, STAT3, JAK2, and INF-γ in clinical samples and mice were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The positive rate of autologous serum skin test and the histamine release rate of CSU patients, compared with normal subjects, were apparently elevated. Compared with controls, mice with CSU experienced longer duration and higher frequency of pruritus and demonstrated enhanced levels of CD8 + , the ratio of CD4 + /CD8 + , number of eosinophils, and inflammatory cytokine expression in serum as well as activated JAK/STAT signalling pathway; at the same time, levels of CD4 + and INF-γ were reduced. This trend was found in CSU mice overexpressing IL-9 and IL-10 when compared with the CSU mice without treatment. In contrast, JAK/STAT inhibition reversed the above trend.Overall, our study suggests that IL-9 and IL-10 contribute to CSU development via activation of the JAK/STAT signalling pathway. K E Y W O R D S chronic spontaneous urticaria, inflammation, interleukin-9, interleukin-10, JAK/STAT signalling pathway 1 | INTRODUCTION Chronic urticaria (CU), defined as urticaria that has been continuously or intermittently existing for more than 6 weeks, has an estimated prevalence in the general population of 0.5% to 5% and an incidence of 1.4% per year. 1 Patients where no underlying cause for CU was identified were diagnosed as chronic idiopathic urticaria (mainly used in North America) or chronic spontaneous urticaria (CSU). 2 CSU is caused by degranulation of basophils and/or cutaneous mast cells, which results in effective vasoactive mediators released to induce vasodilatation and increased capillary permeability, leading to erythema and wheal formation. 3 Wheal is an elementary dermatological lesion, characterized by itchiness and the presences of central oedema in various sizes, with a reflex erythema encircling and ephemeral

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Abnormal repression of SHP-1, SHP-2 and SOCS-1 transcription sustains the activation of the JAK/STAT3 pathway and the progression of the disease in multiple myeloma

Cited by 35 publications

References 51 publications

Abnormal PTBP1 Expression Sustains the Disease Progression of Multiple Myeloma

Abnormal PTBP1 Expression Sustains the Disease Progression of Multiple Myeloma

The Roles of Protein Tyrosine Phosphatases in Hepatocellular Carcinoma

Role of IL‐9 and IL‐10 in the pathogenesis of chronic spontaneous urticaria through the JAK/STAT signalling pathway

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