Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing Protein Family in Hepatocellular Carcinoma

Cho, Sang Yeon; Kim, Sung-Ha; Son, Mi Ju; Rou, Woo Sun; Kim, Seok Hyun; Eun, Hyuk Soo; Lee, Byung Seok

doi:10.1007/s10620-018-5307-x

Cited by 24 publications

(20 citation statements)

References 27 publications

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“…TXNIP expression in vitro inhibited hepatocellular carcinoma cell proliferation and induced apoptosis 80 . Thus, prolonged Gm15441-mediated suppression of TXNIP may also contribute to PPARα agonist induced hepatocellular carcinoma 81 .…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

et al. 2020

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Exploring the molecular mechanisms that prevent inflammation during caloric restriction may yield promising therapeutic targets. During fasting, activation of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) promotes the utilization of lipids as an energy source. Herein, we show that ligand activation of PPARα directly upregulates the long non-coding RNA gene Gm15441 through PPARα binding sites within its promoter. Gm15441 expression suppresses its antisense transcript, encoding thioredoxin interacting protein (TXNIP). This, in turn, decreases TXNIP-stimulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, caspase-1 (CASP1) cleavage, and proinflammatory interleukin 1β (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 PPARα agonism and fasting. These findings provide evidence for a mechanism by which PPARα attenuates hepatic inflammasome activation in response to metabolic stress through induction of lncRNA Gm15441.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

et al. 2020

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“…Previous studies identified TXNRD1 as a regulator of endocellular oxidative stress and a promoter of tumor development [23, 24], with irreversible suppression of cytoplasmic TXNRD1 levels demonstrated as a novel direction for cancer treatment [11, 25, 26]. Additionally, studies reported that TXNRD1 levels are upregulated in HCC and negatively correlated with HCC-patient prognosis [27, 28]. In the present study, our data demonstrated that TXNRD1 promoted the proliferation, migration, and invasion of HCC cells, which provided insight into the previously unknown molecular mechanisms associated with TXNRD1 in HCC.…”

Section: Discussionmentioning

confidence: 99%

miR-125b-5p inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma via targeting TXNRD1

et al. 2019

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Background Thioredoxin reductase 1 ( TXNRD1 ) is an antioxidant enzyme reportedly overexpressed in hepatocellular carcinoma (HCC); however, the detailed function and mechanisms of TXNRD1 in HCC remain obscure. In this study, we investigated the miR-125b-5p-specific regulation of TXNRD1 levels and its effect on HCC cells. Methods We detected miR-125b-5p levels in human HCC tissue samples through quantitative reverse transcription polymerase chain reaction (qRT-PCR), and in vitro experiments were employed to investigate the effect of miR-125b-5p on HCC cell proliferation, migration, and invasion. Additionally, we examined miR-125b-5p-mediated changes in TXNRD1 levels by qRT-PCR and western blotting, and a dual luciferase-reporter assay was conducted to confirm direct targeting of the 3′ untranslated region of TXNRD1 mRNA by miR-125b-5p. Results miR-125b-5p expression was reduced in HCC tissues relative to that in matched para-carcinoma tissues; this finding was verified in HCC cohorts from the Gene Expression Omnibus and The Cancer Genome Atlas. Additionally, low miR-125b-5p expression was associated with poor prognosis in HCC patients, and gene-set enrichment analysis indicated that miR-125b-5p levels were associated with HCC proliferation and metastasis. As predicted, overexpressing miR-125b-5p restrained the proliferation, migration, and invasion of Huh7 and SK-Hep-1 cells and forced expression of the miR-125b-5p-downregulated TXNRD1 mRNA and protein levels in HCC cells. Moreover, dual luciferase-reporter assays revealed that miR-125b-5p targets TXNRD1 to directly regulate its expression, whereas TXNRD1 overexpression abolishes the inhibitory effect of miR-125b-5p on HCC cell proliferation, migration, and invasion. Conclusions These results demonstrated miR-125b-5p as a tumor suppressor in HCC through its inhibition of TXNRD1 , thereby suggesting it as a potential target for the clinical treatment of HCC. Electronic supplementary material The online version of this article (10.1186/s12935-019-0919-6) contains supplementary material, which is available to authorized users.

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“…Members of this calcium-dependent phospholipid-binding protein family play a role in the regulation of cell growth and signal transduction pathways. ANXA2 has been reported to be associated with cervical, gastric, colorectal, ovarian, and liver cancers [27,28].…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognostic Candidate Genes in Breast Cancer by Integrated Bioinformatic Analysis

Wang

Cai

et al. 2019

JCM

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Breast cancer is one of the most common malignancies. However, the molecular mechanisms underlying its pathogenesis remain to be elucidated. The present study aimed to identify the potential prognostic marker genes associated with the progression of breast cancer. Weighted gene coexpression network analysis was used to construct free-scale gene coexpression networks, evaluate the associations between the gene sets and clinical features, and identify candidate biomarkers. The gene expression profiles of GSE48213 were selected from the Gene Expression Omnibus database. RNA-seq data and clinical information on breast cancer from The Cancer Genome Atlas were used for validation. Four modules were identified from the gene coexpression network, one of which was found to be significantly associated with patient survival time. The expression status of 28 genes formed the black module (basal); 18 genes, dark red module (claudin-low); nine genes, brown module (luminal), and seven genes, midnight blue module (nonmalignant). These modules were clustered into two groups according to significant difference in survival time between the groups. Therefore, based on betweenness centrality, we identified TXN and ANXA2 in the nonmalignant module, TPM4 and LOXL2 in the luminal module, TPRN and ADCY6 in the claudin-low module, and TUBA1C and CMIP in the basal module as the genes with the highest betweenness, suggesting that they play a central role in information transfer in the network. In the present study, eight candidate biomarkers were identified for further basic and advanced understanding of the molecular pathogenesis of breast cancer by using co-expression network analysis.

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Clinical Significance of the Thioredoxin System and Thioredoxin-Domain-Containing Protein Family in Hepatocellular Carcinoma

Cited by 24 publications

References 27 publications

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting

miR-125b-5p inhibits cell proliferation, migration, and invasion in hepatocellular carcinoma via targeting TXNRD1

Identification of Prognostic Candidate Genes in Breast Cancer by Integrated Bioinformatic Analysis

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