Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma

Liu, Xiaojia; Sui, Xianxian; Zhang, Can-Jing; Wei, Kelu; Bao, Yun; Xiong, Ji; Zhou, Zhongwen; Chen, Zhongqing; Wang, Chaoqun; Zhu, Hongguang; Tang, Feng

doi:10.7150/jca.36495

Cited by 20 publications

(17 citation statements)

References 29 publications

(30 reference statements)

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“…[144] GSTA1 expression is downregulated in HCC and correlates with poor prognosis. [248] GSTM1 expression is downregulated in HCC.…”

Section: Tumor Typementioning

confidence: 93%

“…In that regard, GPX1, GPX3, and GPX7 expression were found to be decreased [ 144 , 240 , 241 , 242 , 243 ] in tumor tissues, while the expression of GPX2 and GPX4 was found to be upregulated [ 144 , 146 , 244 , 245 , 246 , 247 ]. In addition, GSTA1, GSTM1, and GSTZ1 are reported to be downregulated in tumor tissue and can correlate with a poor prognosis [ 63 , 248 , 249 , 250 , 251 ], while GSTT1, GSTO1, and GSTK1 are mostly reported to be upregulated in tumor tissue compared to the normal surrounding tissue [ 252 , 253 ]. The expression level of GSTP1 in tumor tissue is controversial [ 144 , 253 , 254 , 255 ], and its involvement in tumorigenesis could at least in part depend on its hypermethylation [ 256 , 257 , 258 , 259 , 260 ].…”

Section: Redox Homeostasismentioning

confidence: 99%

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The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

et al. 2020

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Cancer remains an elusive, highly complex disease and a global burden. Constant change by acquired mutations and metabolic reprogramming contribute to the high inter- and intratumor heterogeneity of malignant cells, their selective growth advantage, and their resistance to anticancer therapies. In the modern era of integrative biomedicine, realizing that a personalized approach could benefit therapy treatments and patients’ prognosis, we should focus on cancer-driving advantageous modifications. Namely, reactive oxygen species (ROS), known to act as regulators of cellular metabolism and growth, exhibit both negative and positive activities, as do antioxidants with potential anticancer effects. Such complexity of oxidative homeostasis is sometimes overseen in the case of studies evaluating the effects of potential anticancer antioxidants. While cancer cells often produce more ROS due to their increased growth-favoring demands, numerous conventional anticancer therapies exploit this feature to ensure selective cancer cell death triggered by excessive ROS levels, also causing serious side effects. The activation of the cellular NRF2 (nuclear factor erythroid 2 like 2) pathway and induction of cytoprotective genes accompanies an increase in ROS levels. A plethora of specific targets, including those involved in thioredoxin (TRX) and glutathione (GSH) systems, are activated by NRF2. In this paper, we briefly review preclinical research findings on the interrelated roles of the NRF2 pathway and TRX and GSH systems, with focus given to clinical findings and their relevance in carcinogenesis and anticancer treatments.

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“…[144] GSTA1 expression is downregulated in HCC and correlates with poor prognosis. [248] GSTM1 expression is downregulated in HCC.…”

Section: Tumor Typementioning

confidence: 93%

Section: Redox Homeostasismentioning

confidence: 99%

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

et al. 2020

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“…Additionally, there were multiple collagen genes overly-expressed in HCC mice along with Ly6D, Tff3, and Spink1, which are well known HCC markers [32][33][34][35]. Alongside, Gsta1 and Atf3 were upregulated in HCC mice, which have been proposed as potential tumor suppressors in HCC development [36][37][38][39]. Intriguingly, there were 17 genes associated with the group of major urinary proteins (MUP) that were downregulated in the T5KO-HB mice prone to ICD-induced HCC.…”

Section: Plos Onementioning

confidence: 99%

Fermentable fiber-induced hepatocellular carcinoma in mice recapitulates gene signatures found in human liver cancer

et al. 2020

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Hepatocellular carcinoma (HCC), the most malignant form of primary liver cancer, is the fourth most prevalent cause of cancer mortality globally. It was recently discovered that the dietary fermentable fiber, inulin, can reprogram the murine liver to favor HCC development in a gut microbiota-dependent manner. Determining the molecular pathways that are either over expressed or repressed during inulin-induced HCC would provide a platform of potential therapeutic targets. In the present study, we have combined analysis of the novel inulininduced HCC murine model and human HCC samples to identify differentially expressed genes (DEGs) in hepatocarcinogenesis. Hepatic transcriptome profiling revealed that there were 674 DEGs in HCC mice compared to mice safeguarded from HCC. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis uncovered enrichment in ECMreceptor interaction, steroid hormone biosynthesis, PPAR signaling pathway, focal adhesion and protein digestion and absorption during inulin-induced HCC. Tandem mass tag based quantitative, multiplexed proteomic analysis delineated 57 differentially expressed proteins, where the over-expressed proteins were associated with cell adhesion molecules, valine, leucine and isoleucine degradation and ECM-receptor interaction. After obtaining the human orthologs of the mouse genes, we did a comparison analysis to level 3 RNA-seq data found in the Cancer Genome Atlas (TCGA) database, corresponding to human HCC (n = 361) and healthy liver (n = 50) samples. Out of the 549 up-regulated and 68 down-regulated human orthologs identified, 142 genes (137 significantly over-expressed and 5 significantly under-expressed) were associated with human HCC. Using univariate survival analysis, we found 27 over-expressed genes involved in cell-cell adhesion and cell division

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“…Furthermore, poor prognosis in patients with HCC is related to the aberrant expression of several metabolismrelated genes. 9,[19][20][21] This suggests that metabolic reprogramming in HCC may serve as a novel therapeutic target for the disease.…”

Section: Introductionmentioning

confidence: 99%

<p>Glucosamine-6-Phosphate Isomerase 1 Promotes Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma</p>

Cheng

Zheng

et al. 2020

CMAR

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Purpose: Reprogramming of metabolic pathways is a hallmark of the pathological changes that occur in cancer cells. Under physiological conditions, glucosamine-6-phosphate isomerase 1 (GNPDA1) promotes the conversion of the hexosamine system to the glycolytic pathway and may, therefore, affect energy metabolism. Low expression of GNPDA1 has been reported in normal liver tissues, however, analysis of the hepatocellular carcinoma (HCC) database in The Cancer Genome Atlas (TCGA) revealed that GNPDA1 was highly expressed in HCC tissues. The purpose of this study was to explore the role of GNPDA1 in HCC. Patients and Methods: We analyzed the expression of GNPDA1 in HCC tissues as well as the clinical outcomes of HCC patients with high or low expression of GNPDA1. Furthermore, the relationship between the expression of GNPDA1 and advanced tumor stage, TNM stage, grade, gender, or metastasis was assessed using high-throughput RNA sequencing data from TCGA HCC cohort and Kaplan-Meier survival analysis. The expression of GNPDA1 in HCC and normal liver cell lines was subsequently detected by qRT-PCR and Western blot analysis. Additionally, the effects of GNPDA1 knockdown in SMMC-7721 and Huh7 cell lines were examined. Cell proliferation, migration, invasion, and apoptosis following knockdown were investigated by the MTT assay and EdU, cell cycle, apoptosis, transwell, and wound healing analyses. Results: There was a significant association between high GNPDA1 expression and advanced tumor stage, TNM stage or grade, but not with gender. High GNPDA1 expression was associated with poor prognosis in patients with HCC. Furthermore, the MTT assay and EdU, cell cycle, apoptosis, wound healing, and transwell analyses revealed that GNPDA1 promoted the proliferation, migration, and invasion of HCC cells and inhibited apoptosis. Conclusion: The results of this study suggest that GNPDA1 may serve as a novel prognostic biomarker and therapeutic target for HCC.

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Glutathione S-transferase A1 suppresses tumor progression and indicates better prognosis of human primary hepatocellular carcinoma

Cited by 20 publications

References 29 publications

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

Fermentable fiber-induced hepatocellular carcinoma in mice recapitulates gene signatures found in human liver cancer

<p>Glucosamine-6-Phosphate Isomerase 1 Promotes Tumor Progression and Indicates Poor Prognosis in Hepatocellular Carcinoma</p>

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