JAK2/STAT3 in role of arsenic-induced cell proliferation: a systematic review and meta-analysis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shugang Li ◽  
Shanshan Ran ◽  
Qingxin Ren
Keyword(s):  
Cell Proliferation ◽  
Meta Analysis ◽  
Arsenic Concentration ◽  
Arsenic Exposure ◽  
Malignant Cell ◽  
Dose Effect ◽  
Expression Level ◽  
Exposure Concentration ◽  
Effect Relationship

Abstract Objectives Malignant cell proliferation is one of the important mechanisms of arsenic poisoning. A large number of studies have shown that STAT3 plays an important role in cell malignant proliferation, but there are still many contradictions in the effect of arsenic on JAK2/STAT3. This study aims to explore the role of JAK2/STAT3 in arsenic-induced cell proliferation. Methods By taking normal cells as the research object and using Standard Mean Difference (SMD) as the effect size, meta-analysis was used to explore the effect of arsenic on JAK2/STAT3. Then, the dose-effect Meta was used to further clarify the dose-effect relationship of arsenic on JAK2/STAT3. Results Through meta-analysis, this study found that arsenic could promote the phosphorylation of STAT3 (SMD=4.21, 95%CI [1.05, 7.37]), and increase IL-6 and p-JAK2, Vimentin, VEGF expression levels, thereby inducing malignant cell proliferation. In addition, this study also found that arsenic exposure dose (<5 μmol m−3), time(<24 h) and cell type were important sources of heterogeneity in the process of exploring the effects of arsenic on p-STAT3, IL-6 and p-JAK2. Dose-effect relationship meta-analysis results showed that arsenic exposure significantly increased the expression level of IL-6. When the arsenic exposure concentration was less than 7 μmol m−3, the expression level of p-JAK2 upregulated significantly as the arsenic exposure concentration gradually increasing. Moreover, the expression level of p-STAT3 elevated significantly with the gradual increase of the arsenic concentration under 5 μmol m−3 of arsenic exposure, but the expression level of p-STAT3 gradually decreases when the concentration is greater than 5 μmol m−3. Conclusions Exposure to low dose of arsenic could promote the expression of JAK2/STAT3 and induce the malignant proliferation of cells through upregulating IL-6, and there was dose-effect relationship among them.

scholarly journals Tau: At the Interface Between Neurodegeneration and Cancer?

2020 ◽  
Author(s):  
Stéphanie Papin ◽  
Paolo Paganetti
Keyword(s):  
Meta Analysis ◽  
Expression Level ◽  
Cancer Type ◽  
Cancer Resistance ◽  
Tumor Cell Death ◽  
Microtubule Network ◽  
Related Disorder ◽  
P53 Signaling ◽  
Tau Expression

For its microtubule-binding properties, the expression level of the neurodegeneration-associated protein Tau is pondered as a potential modifier of cancer resistance to chemotherapy since decades. Indeed, Tau binds microtubules at the same site as taxanes, a class of chemotherapeutic drugs designed to stabilize the microtubule network in order to stall cell division and to induce tumor cell death. Whilst independent studies report the association between low Tau expression and superior taxane response, the data were refused by a meta-analysis, suggesting interference of other parameters. Unpredictably, Tau expression level was identified as a prognostic cancer marker, whereby its positive or negative predictive value for survival depended on the cancer type. With recent experimental evidence linking Tau to P53 signaling, DNA stability and protection and to the implication of Tau in cancer is strengthened. The identification of a role of Tau at the interface between two major aging-related disorder families, neurodegeneration and cancer, offers clues for the epidemiological observation inversely correlating these disorders. Elucidating how Tau is mechanistically implicated in cellular pathways common to these devastating illnesses may extend the Tau-targeting therapeutic opportunities to cancer.

scholarly journals Prognosis Value of Low microRNA-34a Expression in Human Gastrointestinal Cancer: A Meta-Analysis

2020 ◽  
Author(s):  
Yan-Ling Chen ◽  
Xiao-Lin Liu ◽  
Ling Li
Keyword(s):  
Meta Analysis ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Cancer Prognosis ◽  
Expression Level ◽  
Significant Relation ◽  
Free Survival ◽  
Predictive Role ◽  
Disease Free

Abstract Background: Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs). Methods: All the eligible studies were searched by PubMed, Web of Science and EMBASE and survival results were extracted. Then, the hazard ratio (HR) with corresponding 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratio (OR) and 95%CIs. Results: A total of 20 studies were included in this meta-analysis. For overall survival (OS), the lower miR-34a expression significantly predicted poorer outcome in GICs, with the pooled HR of 1.86 (95% CI: 1.52-2.28, P<0.01). For disease-free survival (DFS), progressive-free survival (PFS), and recurrence-free survival (RFS), the lower miR-34a expression revealed worse DFS/PFS/RFS with the pooled HR of 1.86 (95% CI: 1.31–2.63, P < 0.01). Significant relation of differentiation/TMN stage/lymphatic metastasis and the expression level of miR-34a was identified. Conclusion: This meta-analysis reveals that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS of GICs patients. In addition, miR-34a expression level is relatively lower in patients with lymph node metastasis than patients without, and decreased miR-34a expression level is linked to poor tumor differentiation and late TMN stage. MiR-34a may become a new factor for prognosis prediction and progression of GICs.

scholarly journals RETRACTED ARTICLE: Oncogenic transformation of human lung bronchial epithelial cells induced by arsenic involves ROS-dependent activation of STAT3-miR-21-PDCD4 mechanism

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Poyil Pratheeshkumar ◽  
Young-Ok Son ◽  
Sasidharan Padmaja Divya ◽  
Lei Wang ◽  
Zhuo Zhang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Cell Transformation ◽  
Arsenic Exposure ◽  
Malignant Cell ◽  
Bronchial Epithelial ◽  
Signaling Axis ◽  
Retracted Article ◽  
Programmed Cell Death 4 ◽  
Malignant Cell Transformation

Abstract Arsenic is a well-documented human carcinogen. The present study explored the role of the onco-miR, miR-21 and its target protein, programmed cell death 4 (PDCD4) in arsenic induced malignant cell transformation and tumorigenesis. Our results showed that treatment of human bronchial epithelial (BEAS-2B) cells with arsenic induces ROS through p47phox, one of the NOX subunits that is the key source of arsenic-induced ROS. Arsenic exposure induced an upregulation of miR-21 expression associated with inhibition of PDCD4, and caused malignant cell transformation and tumorigenesis of BEAS-2B cells. Indispensably, STAT3 transcriptional activation by IL-6 is crucial for the arsenic induced miR-21 increase. Upregulated miR-21 levels and suppressed PDCD4 expression was also observed in xenograft tumors generated with chronic arsenic exposed BEAS-2B cells. Stable shut down of miR-21, p47phox or STAT3 and overexpression of PDCD4 or catalase in BEAS-2B cells markedly inhibited the arsenic induced malignant transformation and tumorigenesis. Similarly, silencing of miR-21 or STAT3 and forced expression of PDCD4 in arsenic transformed cells (AsT) also inhibited cell proliferation and tumorigenesis. Furthermore, arsenic suppressed the downstream protein E-cadherin expression and induced β-catenin/TCF-dependent transcription of uPAR and c-Myc. These results indicate that the ROS-STAT3-miR-21-PDCD4 signaling axis plays an important role in arsenic -induced carcinogenesis.

scholarly journals 17β-Estradiol promotes cell proliferation in rat osteoarthritis model chondrocytes via PI3K/Akt pathway

2011 ◽  
Vol 16 (4) ◽  
Author(s):  
Jia Huang ◽  
Chun Xia ◽  
Xin Zheng ◽  
Ting Yi ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Expression Level ◽  
Akt Pathway ◽  
Chondrocyte Proliferation ◽  
Common Cause ◽  
Akt Activation ◽  
17Β Estradiol ◽  
Oa Chondrocytes ◽  
The Relationship

AbstractOsteoarthritis (OA) is the most common cause of musculoskeletal pain and disability. The importance of chondrocytes in the pathogenesis of OA is unequivocal. 17β-estradiol (E2) has a potential protective effect against OA. However, the mechanism of E2 in OA chondrocytes remains unclear. In this study, we investigated the regulative effect of E2 on cell growth and the relationship between E2 and the PI3K/Akt pathway in rat OA model chondrocytes (pretreated with interleukin-1β). We found that E2 induced chondrocyte proliferation, and increased the expression level of Akt simultaneously, especially the expression level of P-Akt. Furthermore, the inhibition of P-Akt could block chondrocyte proliferation induced by E2. These results suggest that PI3K/Akt activation induced by E2 may be an important factor in the mechanism of E2 in cell proliferation in rat OA model chondrocytes, and help further understanding the role of E2 in OA progression.

scholarly journals The Association between Chronic Arsenic Exposure and Hypertension: A Meta-Analysis

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Tanvir Abir ◽  
Bayzidur Rahman ◽  
Catherine D'Este ◽  
Abdulaziz Farooq ◽  
Abul Hasnat Milton
Keyword(s):  
Cohort Studies ◽  
Odds Ratio ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Arsenic Concentration ◽  
Arsenic Exposure ◽  
Small Sample ◽  
Odds Ratios ◽  
Cross Sectional ◽  
Chronic Arsenic Exposure

Background. There is inconclusive evidence from cross-sectional and cohort studies that arsenic exposure is a risk factor involved in the development of hypertension.Methods. A database search, using several keywords, was conducted to identify relevant studies. Separate odds ratio estimates for arsenic exposure with concentration only and arsenic exposure with duration, including biomarker, were extracted from studies that met all inclusion criteria. The extracted odds ratios (OR) comparing the highest exposure categories with the lowest in each study were pooled using the random effects methods of meta-analysis. Heterogeneity of odds ratios in the included studies were analyzed using I2statistics.Results. Eight studies were analyzed. Using the exposure as arsenic concentration in the drinking water, the OR estimate was 1.9 (95% CI: 1.2–3.0), with the I2= 92%, while using the exposure as concentration and duration, the OR estimate was 1.4 (95% CI: 0.95–2.0) with the I2= 80%. Meta-regression was done and the quality of exposure measurement was found to be significantly associated with the effect measure. For a one unit increase in the score from exposure assessment, the odds ratio decreased by 6%. No publication bias was evident. The only major weaknesses of this study were heterogeneity across studies and small sample size.Conclusions. The study findings provide limited evidence for a relationship between arsenic and hypertension. In summary, the relationship between arsenic exposure and hypertension is still inconclusive and needs further validation through prospective cohort studies.

Inhibition of cell proliferation and induction of apoptosis by N1,N11-diethylnorspermine-induced polyamine pool reduction

2007 ◽  
Vol 35 (2) ◽  
pp. 405-409 ◽  
Author(s):  
S.M. Oredsson ◽  
K. Alm ◽  
E. Dahlberg ◽  
C.M. Holst ◽  
V.M. Johansson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Regulation ◽  
Meta Analysis ◽  
Short Review ◽  
Cell Cycle Kinetics ◽  
Polyamine Analogue ◽  
Induction Of Apoptosis ◽  
Cycle Regulation

Reduction of cellular polyamine pools results in inhibition of cell proliferation and sometimes in induction of cell death. Reduction of cellular polyamine pools can be achieved by several strategies involving all the mechanisms of polyamine homoeostasis, i.e. biosynthesis, catabolism and transport across the cell membrane. In the present paper, we concentrate on results achieved using the polyamine analogue DENSPM (N1,N11-diethylnorspermine) on different cell lines. We discuss polyamine levels in DENSPM-treated cells in relation to effects on cell cycle kinetics and induction of apoptosis. To really understand the role of polyamines in cell cycle regulation and apoptosis, we believe it is now time to go through the vast polyamine literature in a meta-analysis-based manner. This short review does not claim to be such a study, but it is our hope to stimulate such studies in the polyamine field. Such work is especially important from the viewpoint of introducing drugs that affect polyamine homoeostasis in the treatment of various diseases such as cancer.

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