Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation

Su, Cunjin; Shi, Aiming; Cao, Guowen; Tao, Tao; Chen, Ruidong; Hu, Zhanhong; Shen, Zhu; Hong, Tao; Cao, Bin; Hu, Duanmin; Bao, Junjie

doi:10.1016/j.bbrc.2015.03.138

Cited by 29 publications

(22 citation statements)

References 24 publications

(27 reference statements)

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“…It shows aggressive local growth and metastasizes to regional lymph nodes, liver, bone marrow, and bone cortex (Roy Choudhury et al, 2012). Tumors in infants <1 year of age often regress spontaneously and usually have an excellent prognosis, whereas those in older patients are aggressive, leading to a fatal outcome (Su et al, 2015). Despite major advances in therapies, neuroblastoma is still associated with a high morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo

et al. 2017

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Background: Neuroblastoma is the most common extracranial tumors in children. At present about the true etiology of neuroblastoma is unclear and many studies have tried to find effective treatments for these primary malignant tumors. Although it has been illustrated that androgen receptor (AR) was expressed in neuroblastoma cells in some former reports, the biological role of androgen receptor in the development of neuroblastoma is not fully understood.Methods: Androgen (R1881) and the antagonists of androgen receptor (MDV3100 and ARN509) were used to study the role of the androgen receptor signaling pathway in vitro and in vivo on SH-SY5Y and Neuro-2a (N2a) cell lines.Results: We found that AR expression showed an R1881 dose-dependent manner in neuroblastoma cells in vitro and R1881was able to increase, while both antagonists of androgen receptor (MDV3100 and ARN509) significantly decrease, the proliferation, migration, invasion and sphere formation of SH-SY5Y and N2a cells. Moreover, androgen promoted the growth of N2a tumor in vivo. However, when androgen receptor (AR) was effectively knocked down in the two cell lines by siRNA, either promoting or inhibiting effect of the androgen or androgen receptor antagonists, respectively, was attenuated.Conclusion: Our results suggested that androgen receptor may involve in the progression of neuroblastoma as well as provided insight into a new target for the diagnosis and treatment of neuroblastoma patients.

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Section: Introductionmentioning

confidence: 99%

Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo

et al. 2017

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“…Txnip has been considered a tumor suppressor because of suppressed expression in a variety of cancers (reviewed by [ 17 ]). Therefore, there is high therapeutic interest in using small molecules to reactivate Txnip expression as an anticancer strategy [ 37 ]. One speculative growth pathway based on our proteomic data involves Poly ADP-ribose polymerase 1 (PARP1).…”

Section: Discussionmentioning

confidence: 99%

Identification of Redox and Glucose‐Dependent Txnip Protein Interactions

Forred

Neuharth

Kim

et al. 2016

Oxidative Medicine and Cellular Longevity

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Thioredoxin-interacting protein (Txnip) acts as a negative regulator of thioredoxin function and is a critical modulator of several diseases including, but not limited to, diabetes, ischemia-reperfusion cardiac injury, and carcinogenesis. Therefore, Txnip has become an attractive therapeutic target to alleviate disease pathologies. Although Txnip has been implicated with numerous cellular processes such as proliferation, fatty acid and glucose metabolism, inflammation, and apoptosis, the molecular mechanisms underlying these processes are largely unknown. The objective of these studies was to identify Txnip interacting proteins using the proximity-based labeling method, BioID, to understand differential regulation of pleiotropic Txnip cellular functions. The BioID transgene fused to Txnip expressed in HEK293 identified 31 interacting proteins. Many protein interactions were redox-dependent and were disrupted through mutation of a previously described reactive cysteine (C247S). Furthermore, we demonstrate that this model can be used to identify dynamic Txnip interactions due to known physiological regulators such as hyperglycemia. These data identify novel Txnip protein interactions and demonstrate dynamic interactions dependent on redox and glucose perturbations, providing clarification to the pleiotropic cellular functions of Txnip.

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“…Additionally, Txnip expression was attenuated in untreated Ppara -/compared to Ppara +/+ mouse liver, indicating a role for PPARA in maintaining basal expression of Txnip (Figure 2D). Given that Txnip expression can be upregulated in human neuroblastoma cells by the PPARA activator fenofibrate, which suppresses proliferation and migration (Su et al, 2015), the effects of a single dose of WY-14643 on Gm15441…”

Section: Ppara Activationmentioning

confidence: 99%

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to metabolic stress

Brocker

Kim

Melia

et al. 2019

Preprint

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Fasting paradigms elicit a wide-range of health benefits including suppressing inflammation.Exploring the molecular mechanisms that prevent inflammation during caloric restriction may yield promising new therapeutic targets. During fasting, activation of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARA) promotes the utilization of lipids as an energy source. Herein, we show that ligand activation of PPARA directly upregulates the long non-coding RNA gene Gm15441 through binding sites within its promoter. Gm15441 expression suppresses its antisense transcript, encoding thioredoxin interacting protein (TXNIP). This, in turn, decreases TXNIP-stimulated NLRP3 inflammasome activation, caspase-1 (CASP1) cleavage, and proinflammatory interleukin 1 beta (IL1B) maturation. Gm15441-null mice were developed and shown to be more susceptible to NLRP3 inflammasome activation and to exhibit elevated CASP1 and IL1B cleavage in response to metabolic and inflammatory stimuli. These findings provide evidence for a novel mechanism by which PPARA attenuates hepatic inflammasome activation in response to metabolic stress through lncRNA Gm15441 induction. 4Txnip expression in vivo. Gm15441 LSL mice were treated with a PPARA agonist or fasted to assess how loss of Gm15441 impacts hepatic inflammasome activation in response to both pharmacological and physiologically-induced metabolic stress. TXNIP protein, caspase-1 (CASP1) levels, and interleukin 1 beta (IL1B) cleavage were elevated in Gm15441 LSL mice and were further increased by PPARA activation, indicating that this lncRNA plays a major role in attenuating inflammasome activation. Thus, hepatic PPARA directly regulates the lncRNA Gm15441, which in turn suppresses Txnip expression, which attenuates NLRP3 inflammasome activation during periods of metabolic stress. These studies revealed a novel regulatory mechanism supporting the beneficial effects of fasting, namely, reduced inflammation. Results LncRNA regulation by PPARA is highly tissue-specificTo assess the regulation of lncRNAs by PPARA, RNA-seq was performed using total liver RNA isolated from Ppara +/+ mice, both with and without dietary exposure to the PPARA agonist WY-14643. A lncRNA discovery pipeline was implemented that identified 15,558 liver-expressed lncRNA genes. Of these, 13,343 were intergenic, 1,966 were antisense, and 249 were intragenic lncRNAs. 44% of the 15,558 liver-expressed lncRNAs are considered novel (Melia and Waxman, 2019). Differential gene expression analysis revealed that a total of 1,735 RefSeq genes and 442 liver-expressed lncRNA genes responded to treatment with WY-14643 at an expression foldchange >2 at FDR<0.05, with 968 RefSeq genes and 245 lncRNA genes upregulated, and 767

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Fenofibrate suppressed proliferation and migration of human neuroblastoma cells via oxidative stress dependent of TXNIP upregulation

Cited by 29 publications

References 24 publications

Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo

Androgen Receptor Regulates the Growth of Neuroblastoma Cells in vitro and in vivo

Identification of Redox and Glucose‐Dependent Txnip Protein Interactions

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to metabolic stress

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