TXNIP overexpression suppresses proliferation and induces apoptosis in SMMC7221 cells through ROS generation and MAPK pathway activation

Li, Jian; Yue, Zhongyi; Xiong, Wancheng; Sun, Pengxiao; You, Kun; Wang, Jianguo

doi:10.3892/or.2017.5577

Cited by 52 publications

(37 citation statements)

References 40 publications

(39 reference statements)

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“…S1). TXNIP is involved in redox regulation and acts as a negative regulator of glycolysis [23,[40][41][42][43]. To assess whether BRG1 regulated a STAT3 pathway leading to TXNIP upregulation, lysates from control (scrambled shRNA), and BRG1-KD GBM6 and X16 GICs were prepared and immunoblotted.…”

Section: Brg1 Regulates An Stat3/txnip Pathwaymentioning

confidence: 99%

Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells

et al. 2018

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Glioblastoma multiforme (GBM) is a highly aggressive and malignant brain tumor that is refractory to existing therapeutic regimens, which reflects the presence of stem-like cells, termed Glioma-Initiating Cells (GICs). The complex interactions between different signaling pathways and epigenetic regulation of key genes may be critical in the maintaining GICs in their stem-like state. Although several signaling pathways have been identified as being dysregulated in GBM, the prognosis of GBM patients remains miserable despite improvements in targeted therapies. In this report, we identified that BRG1, the catalytic subunit of the SWI/SNF chromatin remodeling complex, plays a fundamental role in maintaining GICs in their stem-like state. In addition, we identified a novel mechanism by which BRG1 regulates glycolysis genes critical for GICs. BRG1 downregulates the expression of TXNIP, a negative regulator of glycolysis. BRG1 knockdown also triggered the STAT3 pathway, which led to TXNIP activation. We further identified that TXNIP is an STAT3-regulated gene. Moreover, BRG1 suppressed the expression of interferon-stimulated genes, which are negatively regulated by STAT3 and regulate tumorigenesis. We further demonstrate that BRG1 plays a critical role in the drug resistance of GICs and in GIC-induced tumorigenesis. By genetic and pharmacological means, we found that inhibiting BRG1 can sensitize GICs to chemotherapeutic drugs, temozolomide and carmustine. Our studies suggest that BRG1 may be a novel therapeutic target in GBM. The identification of the critical role that BRG1 plays in GIC stemness and chemosensitivity will inform the development of better targeted therapies in GBM and possibly other cancers. Stem Cells 2018.

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Section: Brg1 Regulates An Stat3/txnip Pathwaymentioning

confidence: 99%

Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells

et al. 2018

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“…In recent studies, exposure to SiONPs induces an inflammatory response in human lung cells, and this effect is associated with the elevation of the MAPKs signaling pathway [17,18]. In addition, thioredoxin-interacting protein (TXNIP) plays a role as an oxidative stress activator by decreasing the antioxidant activity of thioredoxin (TRX) [19]. A previous study has shown that the downregulation of TXNIP ameliorates inflammatory responses by inhibiting the MAPKs pathway in mice [20].…”

Section: Introductionmentioning

confidence: 99%

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling

Lim

Shin

Seo

et al. 2020

Cells

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Silica dioxide nanoparticles (SiONPs) have been applied to several fields, such as drug delivery and gene therapy. However, SiONPs are a constituent of fine dust and can induce excessive inflammatory responses in the lungs via the airways. Silibinin, a major component of silymarin, has been known for its anti-oxidant and anti-inflammatory effects. In the present study, we explored the protective effects of silibinin against SiONPs-induced airway inflammation and explored its underlying mechanism of action, focusing on thioredoxin-interacting protein (TXNIP)/mitogen-activated protein kinases (MAPKs) in vitro and in vivo. In SiONPs-stimulated NCI-H292 airway epithelial cells, silibinin treatment effectively suppressed the elevation of the mRNA expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β, which was accompanied by the reduction in the expression of TXNIP, MAPKs, and activator protein-1 (AP-1). In SiONPs-treated mice, silibinin administration inhibited the increase in inflammatory cell counts and proinflammatory mediators, and it alleviated airway inflammation by SiONPs exposure. In addition, silibinin administration effectively suppressed the elevation of TXNIP/MAPKs/AP-1 signaling by SiONPs exposure. Taken together, silibinin effectively inhibited SiONPs-induced inflammatory responses, and this effect was closely related to the inhibition of TXNIP/MAPK/AP-1 signaling. These results suggested that silibinin might be useful for reducing pulmonary inflammation induced by SiONPs.

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“…Loss of TXNIP expression was reported to be associated with the development of some solid tumors [12]. In the breast, high expression of TXNIP was reported in normal breast tissues [13] and showed reduced immunointensity in invasive tumors [14]. Ectopic expression of TXNIP in the breast cancer cell line MCF-7 drives cells to undergo senescence, accompanied by increased reactive oxygen species release.…”

Section: Introductionmentioning

confidence: 99%

Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ

et al. 2018

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Current clinicopathological parameters are useful predictors of breast ductal carcinoma in situ behavior, but they are insufficient to define high-risk patients for disease progression precisely. Thioredoxin-interacting protein (TXNIP) is a key player of oxidative stress. This study aims to evaluate the role of TXNIP as a predictor of ductal carcinoma in situ progression. Tissue microarrays from 776 pure ductal carcinoma in situ and 239 mixed ductal carcinoma in situ and invasive tumors were constructed. All patients were treated at a single institution with a long-term follow-up and TXNIP expression was assessed using immunohistochemistry. TXNIP expression was investigated in terms of associations with clinicopathological and molecular features and patient outcome. Loss/reduced cytoplasmic expression of TXNIP was associated with features of aggressiveness including high nuclear grade (p = 1.6 × 10), presence of comedo necrosis (p = 0.001), and estrogen receptor negative (ER-)/HER2- ductal carcinoma in situ (p = 4.6 × 10). Univariate analysis showed an inverse association between TXNIP expression and outcome in terms of shorter local recurrence-free survival (p = 0.009). Multivariable analyses showed that independent predictors of ductal carcinoma in situ recurrence were low TXNIP expression (p = 0.005, HR = 0.51, and 95% CI: 0.32-0.81), larger ductal carcinoma in situ size, and high nuclear grade. TXNIP functions as a tumor suppressor gene with loss of its expression associated with ductal carcinoma in situ recurrence. TXNIP can be used as a potentially useful marker in prognostic stratification of ductal carcinoma in situ for management decisions.

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TXNIP overexpression suppresses proliferation and induces apoptosis in SMMC7221 cells through ROS generation and MAPK pathway activation

Cited by 52 publications

References 40 publications

Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells

Chromatin Remodeling Factor BRG1 Regulates Stemness and Chemosensitivity of Glioma Initiating Cells

Silibinin Attenuates Silica Dioxide Nanoparticles-Induced Inflammation by Suppressing TXNIP/MAPKs/AP-1 Signaling

Thioredoxin-interacting protein is an independent risk stratifier for breast ductal carcinoma in situ

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