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

Shanshan Ran; Qingxin Ren; Shugang Li

doi:10.1515/reveh-2021-0051

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.

Keywords: arsenic; JAK2/STAT3; malignant proliferation; meta-analysis

Corresponding author: Shugang Li, Department of Child, Adolescent Health and Maternal Health, School of Public Health, Capital Medical University, Beijing 100069, China, Phone: 13661170705, E-mail: lishugang@ccmu.edu.cn

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 81760584

Acknowledgments

This study would like to thank Professor Shugang Li for his guidance, thank research team for their selfless help and I would like to thank Professor Azeem for his help in writing.

Research funding: This work was supported by grants from the National Natural Science Foundation of China (81760584).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The conducted research is not related to either human or animal use.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/reveh-2021-0051).

Received: 2021-04-20

Accepted: 2021-07-07

Published Online: 2021-07-29

Published in Print: 2022-09-27

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Supplementary Material