A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway

Li, Dongjie; Wei, Yongzhong; Xu, Shangzhi; Niu, Qiang; Zhang, Mei; Li, Shugang; Jing, Mingxia

doi:10.3892/mmr.2018.8383

Cited by 8 publications

(8 citation statements)

References 32 publications

(24 reference statements)

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“…ERK is an important member of the mitogen-activated protein kinase (MAPK) family and plays an important role in regulating different biological processes in different cells, including proliferation, differentiation, survival and apoptosis (16). The results of the present study indicated that the activation of the ERK signaling pathway exerted anti-apoptotic ERK protein may be a regulatory target for miR-302d-3p.…”

Section: Discussionmentioning

confidence: 58%

miR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway

Liao¹,

Qiu

Bai

2021

Mol Med Rep

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MicroRNAs (miRs/miRNAs) play important roles in the occurrence, metastasis and prognosis of multiple types of cancers. However, the specific role of miR-302d-3p and its underlying mechanism in breast cancer (BC) have not yet been reported. The present study aimed to identify the role of miR-302D-3p in BC and its potential mechanism using BC cell lines MCF7 and MDA-MB-231 and normal breast epithelial cell MCF-10A. Cancer and paracancerous tissue from patients with BC were also used. Reverse transcription-quantitative PCR was performed to detect the expression of miR-302d-3p and transmembrane Bax inhibitor motif containing 6 (TMBIM6). Dual-luciferase reporter assays verified the binding sites of miR-302d-3p and TMBIM6. Immunohistochemistry was used to measure the expression of TMBIM6. Cell transfection techniques were used to overexpress or interfere with miR-302d-3p and TMBIM6. A Cell Counting Kit-8 assay was performed to detect cell viability, and migration was measured using a wound healing assay. Apoptosis was detected by flow cytometry. The expression levels of apoptosis-related proteins and pathway-related proteins were detected by western blotting. The expression of miR-302d-3p in BC cell lines was found to be downregulated. It was also demonstrated that miR-302d-3p could inhibit cell viability and migration and promote apoptosis. The expression of TMBIM6 in BC cell lines and tissues was upregulated. Upregulated miR-302d-3p was shown to inhibit viability and migration, and promote apoptosis by targeting TMBIM6, during which extracellular signal-regulated kinase (ERK) and its phosphorylation were inhibited in the ERK signaling pathway in cells. Overall, the present study demonstrated that miR-302d-3p could regulate the viability, migration and apoptosis of BC cells through regulating TMBIM6-mediated ERK signaling pathway.

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Section: Discussionmentioning

confidence: 58%

miR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway

Liao¹,

Qiu

Bai

2021

Mol Med Rep

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“…The metal-activated mediators leading to ERK1/2 phosphorylation can be cell-specific and dose-dependent: at 1 mM, W activated the BKαβ1 channels and ERK1/2 phosphorylation in HEK cells [105], but at 30 nM it had no effect on BKαβ1-mediated ERK1/2 activation in human thyrospheres [61]. Moreover, the metal dose may have bidirectional effects on ERK1/2 signaling, as documented for various metals [106,107]. Similar bidirectional effects may also depend on short-or long-term exposure to toxic metals [107], indicating that the final biological effect depends on the magnitude and duration of the exposure: the cell-metal interaction will cause either the predominance of detoxification and cell adaptive processes allowing (deregulated) survival or, when cell defenses are overwhelmed, may lead to cell death.…”

Section: Molecular Mechanisms Of Actionmentioning

confidence: 93%

“…Moreover, the metal dose may have bidirectional effects on ERK1/2 signaling, as documented for various metals [106,107]. Similar bidirectional effects may also depend on short-or long-term exposure to toxic metals [107], indicating that the final biological effect depends on the magnitude and duration of the exposure: the cell-metal interaction will cause either the predominance of detoxification and cell adaptive processes allowing (deregulated) survival or, when cell defenses are overwhelmed, may lead to cell death.…”

Section: Molecular Mechanisms Of Actionmentioning

confidence: 97%

Heavy Metals in the Environment and Thyroid Cancer

Gianì

Masto

Trovato

et al. 2021

Cancers

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In recent decades, the incidence of thyroid cancer has increased more than most other cancers, paralleling the generalized worldwide increase in metal pollution. This review provides an overview of the evidence supporting a possible causative link between the increase in heavy metals in the environment and thyroid cancer. The major novelty is that human thyroid stem/progenitor cells (thyrospheres) chronically exposed to different metals at slightly increased environmentally relevant concentrations show a biphasic increase in proliferation typical of hormesis. The molecular mechanisms include, for all metals investigated, the activation of the extracellular signal-regulated kinase (ERK1/2) pathway. A metal mixture, at the same concentration of individual metals, was more effective. Under the same conditions, mature thyrocytes were unaffected. Preliminary data with tungsten indicate that, after chronic exposure, additional abnormalities may occur and persist in thyrocytes derived from exposed thyrospheres, leading to a progeny population of transformation-prone thyroid cells. In a rat model predisposed to develop thyroid cancer, long-term exposure to low levels of metals accelerated and worsened histological signs of malignancy in the thyroid. These studies provide new insight on metal toxicity and carcinogenicity occurring in thyroid cells at a low stage of differentiation when chronically exposed to metal concentrations that are slightly increased, albeit still in the “normal” range.

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“…Publication bias was evaluated by visually assessing the asymmetry of an inverted funnel plot, and then was supported quantitatively by Begg and Egger tests. [29,31]…”

Section: Methodsmentioning

confidence: 99%

Metallothioneins may be a potential prognostic biomarker for tumors

Wang

Xin²,

Lin³

et al. 2018

Medicine

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Background:Metallothioneins (MTs) were reported to be associated with many kinds of tumors’ prognosis, although MTs expression varied greatly among tumors. To assess the prognostic value of Metallothioneins (MTs) in different kinds of tumors, comprehensive literature search was conducted to perform a meta-analysis.Methods:Eligible studies were identified by PubMed, MEDLINE, Web of Science (WOS), the Cochrane Library of Systematic Reviews, EMBASE, China National Knowledge Infrastructure (CNKI), WANFANG database and SinoMed database up to December 2017, which was designed to assess the prognostic value of MTs in different kinds of tumors. The main endpoint events were overall survival (OS) and disease-free survival (DFS). Hazard ratios (HRs) and its variance were retrieved from the original studies directly or calculated using Engauge Digitizer version 4.1. Random or fixed effects model meta-analysis was employed depending on the heterogeneity. Publication bias was evaluated by funnel plots, Begg and Egger tests.Results:A total of 22 studies were enrolled in this meta-analysis, including 2843 tumor tissues (1517 were MTs negative/low, and 1326 were MTs high). Results showed that there was significant association between MTs expression and tumors’ OS (HR = 1.60; 95%CI 1.34∼1.92, P < .00001). Subgroup analysis showed that high level of MTs expression was associated with prolonged OS in liver cancer (HR = 0.65, 95%CI 0.48∼0.89, P = .007), but it was on the contrary in the tumor of ovary (HR = 1.47, 95%CI 1.01∼2.14, P = .04), bladder (HR = 1.71, 95%CI 1.21∼2.42, P = .002), intestine (HR = 3.13, 95%CI 1.97∼4.97, P < .00001), kidney (HR = 3.31, 95%CI 1.61∼6.79, P = .001). However, there was no significant association between MTs expression and OS in breast (HR = 1.02, 95%CI 0.69∼1.51, P = .93).Conclusions:MTs could be taken as a potential prognostic biomarker for tumors, and uniqueness of MTs prognostic value in liver cancer deserved further study.

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A systematic review and meta-analysis of bidirectional effect of arsenic on ERK signaling pathway

Cited by 8 publications

References 32 publications

miR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway

miR‑302d‑3p regulates the viability, migration and apoptosis of breast cancer cells through regulating the TMBIM6‑mediated ERK signaling pathway

Heavy Metals in the Environment and Thyroid Cancer

Metallothioneins may be a potential prognostic biomarker for tumors

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