<scp>NFAT</scp>c1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL‐mediated extrinsic signaling pathway

Xu, Shiqi; Shu, Penghao; Zou, Song; Shen, Xiaofeng; Qu, Yuanqian; Zhang, Yong; Sun, Kang; Zhang, Jin

doi:10.1002/cam4.1716

Cited by 26 publications

(23 citation statements)

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“…Activator protein-1 (AP-1) is encoded by the FOS gene and is related to the control of a variety of cancer cells, such as breast cancer [ 39 ] and gastric cancer [ 2 ]. The expression level of NFATC1 was decreased in HCC tissues [ 40 ] and was significantly upregulated in ovarian cancer [ 41 ]. However, more recent findings shed light on the mechanism between FOS, NFATC1, and radiotherapy, which have not been systematically discussed.…”

Section: Discussionmentioning

confidence: 99%

Genes Involved in the PD-L1 Pathway Might Associate with Radiosensitivity of Patients with Gastric Cancer

Yan

et al. 2020

Journal of Oncology

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The PD-1/PD-L1 pathway plays an important role in the treatment of cancers as immune checkpoint. However, the association of genes involved in the PD-L1 pathway and radiosensitivity of gastric cancer has not been fully characterized. This study aims to explore the relationship between the expression levels of genes involved in the PD-L1 pathway and radiosensitivity for gastric cancer patients. A total of 367 patients with clinical survival information and radiotherapy information were obtained in The Cancer Genome Atlas (TCGA). Genes involved in the PD-L1 pathway were categorized into high and low expression level groups according to the median value. The Cox proportional hazards model was used to find the association between gene expression level and radiosensitivity. The results show that high expression levels of CD274, EGFR, RAF1, RPS6KB1, PIK3CA, MTOR, CHUK, NFKB1, TRAF6, FOS, NFATC1, and HIF1A were associated with radiosensitivity of gastric cancer. While low expression level of HRAS was also associated with radiosensitivity in gastric cancer. The rates of a new tumor event and disease progression were lower for radiosensitivity patients than other patients. The relationship between the expression level of CD274 and other genes involved in the PD-L1 pathway is significant. GO (Gene Ontology) analysis shows that the biological process of 13 genes was mainly related to innate immune response activating the cell surface receptor signaling pathway. KEGG analysis demonstrated that 13 genes in gastric cancer are mainly related to the PD-L1 expression and PD-1 checkpoint pathway in cancer. The correlation between the expression level of CD274 and other genes involved in the PD-L1 pathway is significant. The present study offered more evidence for using PD-L1 and genes involved in the PD-L1 pathway as potential biomarkers to predict radiosensitive patients with gastric cancer.

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Section: Discussionmentioning

confidence: 99%

Genes Involved in the PD-L1 Pathway Might Associate with Radiosensitivity of Patients with Gastric Cancer

Yan

et al. 2020

Journal of Oncology

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“…Accumulating studies have highlighted that genetic changes and defects in the signaling pathways exert a crucial effect on tumorigenesis and development of HCC, indicating the potential prediction value of molecular biomarkers in HCC prognosis [26]. Furthermore, the prognostic gene signature combined with traditional clinical indicators exhibit a more satisfactory predictive performance than a single parameter [12,27].…”

Section: Discussionmentioning

confidence: 99%

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

et al. 2020

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Purpose: Our study is designed to develop and certify a promising prognostic signature for hepatocellular carcinoma (HCC). Materials and methods: We retrospectively analyzed mRNA expression profiles and clinicopathological data fetched from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. We formulated a prognostic seven-gene signature composed of differentially expressed mRNAs (DEmRNAs) between HCC and nonneoplastic tissues through univariate Cox regression analysis. The receiver operating characteristic (ROC) curve, survival analysis and multivariate Cox regression analysis as well as nomograms were utilized to assess the prognostic performance of the seven-gene signature. Results: The risk score based on a seven-gene signature categorized HCC subjects into a high-and low-risk group. There was significantly discrepant overall survival (OS) between patients in both groups and the corresponding ROC curve revealed a satisfactory predictive performance in HCC survival in both TCGA and GSE76427 cohort. Multivariate Cox regression analysis demonstrated that a seven-gene signature was an independently prognostic factor for HCC. Nomograms combining this prognostic signature with significant clinical characteristics conferred a crucial reference to predict the 1-,3-and 5 years OS. Conclusions: Our study defined a promising seven-gene signature and nomogram model to forecast the OS of HCC patients, which is instrumental in clinical decision and personalized therapy.

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“…Furthermore, NFAT2 participates in the early growth response factor 2 (Egr2)regulated anergic phenotype which impairs the migration and invasion of leukaemia cells [16]. Due to the complex functions of NFAT2, the role of NFAT2 in HCC has not been clearly clarified and the existed research data displays completely opposite effect of NFAT2 in HCC [17,18] Therefore, more research on the effect of NFAT2 in HCC is necessary for profoundly understanding the potential role of NFAT2 in HCC therapy.…”

Section: Introductionmentioning

confidence: 99%

NFAT2 overexpression suppresses the malignancy of hepatocellular carcinoma through inducing Egr2 expression

et al. 2020

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Background Nuclear factor of activated T cells 2 (NFAT2) has been reported to regulate the development and malignancy of few tumors. In this study, we aimed to explore the effect of NFAT2 expression on cell fate of HepG2 cell and its potential mechanisms. Methods Firstly, the pcDNA3.1-NFAT2 plasmid was transfected into HepG2 cells to construct NFAT2 overexpressed HepG2 cells. Then, the chemical count kit-8 cell viability assay, Annexin V-FITC apoptosis detection, EdU labeling proliferation detection, transwell and wound healing experiments were performed. The expression of Egr2 and FasL, and the phosphorylation of AKT and ERK, after ionomycin and PMA co-stimulation, was detected, while the Ca2+ mobilization stimulated by K+ solution was determined. At last, the mRNA and protein expression of NFAT2, Egr2, FasL, COX-2 and c-myc in carcinoma and adjacent tissues was investigated. Results The NFAT2 overexpression suppressed the cell viability, invasion and migration capabilities, and promoted apoptosis of HepG2 cells. NFAT2 overexpression induced the expression of Egr2 and FasL and suppressed the phosphorylation of AKT and ERK. The sensitivity and Ca2+ mobilization of HepG2 cells was also inhibited by NFAT2 overexpression. Compared with adjacent tissues, the carcinoma tissues expressed less NFAT2, Egr2, FasL and more COX-2 and c-myc. Conclusion The current study firstly suggested that NFAT2 suppressed the aggression and malignancy of HepG2 cells through inducing the expression of Egr2. The absence of NFAT2 and Egr2 in carcinoma tissues reminded us that NFAT2 may be a promising therapeutic target for hepatocellular carcinoma treatment.

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NFATc1 is a tumor suppressor in hepatocellular carcinoma and induces tumor cell apoptosis by activating the FasL‐mediated extrinsic signaling pathway

Cited by 26 publications

References 50 publications

Genes Involved in the PD-L1 Pathway Might Associate with Radiosensitivity of Patients with Gastric Cancer

Genes Involved in the PD-L1 Pathway Might Associate with Radiosensitivity of Patients with Gastric Cancer

A novel seven-gene signature as Prognostic Biomarker in Hepatocellular Carcinoma

NFAT2 overexpression suppresses the malignancy of hepatocellular carcinoma through inducing Egr2 expression

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