Dataset Information

Overexpression of modified human TR?1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

ABSTRACT: Association studies suggest that TR?1 functions as a tumor suppressor. Thyroid hormone receptors (TRs) mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). We previously constructed an artificially modified human TR?1 (m-TR?1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TR?1 (TR?1) DBD. Studies confirmed that m-TR?1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vitro. To understand the role of m-TR?1 in liver tumor development, we adopted a gain-of-function approach by stably expressing TR? (m-TR?1 and TR?1) genes in a human hepatocarcinoma cell line, SK-hep1 (without endogenous TR?), and then evaluated the effects of the expressed TR? on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. In the presence of 3,5,3-L-triiodothyronine (T3), the expression of TR? in SK-hep1 cells inhibited cancer cell proliferation and impeded tumor cell migration through the up-regulation of 4-1BB, Caspase-3, and Bak gene expression; down-regulation of Bcl-2 gene expression; and activation of the Caspase-3 protein. TR? expression in SK-hep1 led to less tumor growth in xenograft models. Additionally, the anti-tumor effect of m-TR?1 was stronger than that of TR?1. These data indicate that m-TR?1 can act as a tumor suppressor in hepatocarcinoma and its role was significantly better than that of TR?1.

SUBMITTER: Peng X

PROVIDER: S-EPMC6223806 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Overexpression of modified human TRβ1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Peng Xiaoxiang X Zhou Yuntao Y Sun Yanli Y Song Wei W Meng Xiangying X Zhao Chunling C Zhao Ronglan R

Molecular and cellular biochemistry 20180420 1-2

Association studies suggest that TRβ1 functions as a tumor suppressor. Thyroid hormone receptors (TRs) mediate transcriptional responses through a highly conserved DNA-binding domain (DBD). We previously constructed an artificially modified human TRβ1 (m-TRβ1) via the introduction of a 108-bp exon sequence into the corresponding position of the wild-type human TRβ1 (TRβ1) DBD. Studies confirmed that m-TRβ1 was functional and could inhibit the proliferation of breast cancer MDA-MB-468 cells in vi ...[more]

PMID: 29679278

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Project description:BackgroundFerroptosis plays a vital role in hepatocellular carcinoma (HCC). CISD1 is known to regulate ferroptosis negatively. However, the correlations of CISD1 to prognosis in HCC and its potential mechanism remain unclear.AimTo investigate the expression level and prognostic value of CISD1 in HCC.MethodsGene expression and clinical data for 33 cancer types in TCGA were downloaded from the UCSC Xena platform. Pan-cancer analysis was performed to determine the expression profile and prognostic value of CISD1 in human cancers. GEO datasets and Human Protein Atlas (HPA) were used to verify the mRNA and protein expression levels. The influence of CISD1 on clinical prognosis in HCC was evaluated using a Kaplan-Meier plotter. The PPI network was constructed using the STRING database and Cytoscape. GO and KEGG pathways were constructed using the "clusterProfiler" R package with the FDR cutoff of 0.05. The methylation at the CISD1 promoter was detected using UALCAN and GEO datasets. The correlations between CISD1 and HCC immune infiltrates were investigated via TIMER.ResultsPan-cancer analysis of TCGA data showed that CISD1 is differentially expressed in multiple tumors. Data of gene expression microarrays reveal that the mRNA expression of CISD1 is higher in HCC than that in normal tissue. The protein level of CISD1, validated by the Human Protein Atlas (HPA) database, was upregulated consistently with mRNA levels in HCC samples. High CISD1 expression was associated with better overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and progression-free survival (PFS) in LGG, but with poorer OS, DFS, DSS, and PFS in LIHC. Protein-protein interaction (PPI) analysis and GO/KEGG analysis showed that the PPI network and GO term of CISD1 were mainly associated with energy and iron metabolism. Promoter hypomethylation correlated with overexpression of CISD1. CISD1 expression was positively correlated with infiltrating levels of CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in HCC.ConclusionsThese findings suggest that hypomethylation of the CISD1 promoter increases its expression in HCC. CISD1 is associated with prognosis and immune infiltrating levels of CD8+ T cells, macrophages, neutrophils, and DCs in HCC patients. These findings suggest that CISD1 can be used as a prognostic biomarker for determining prognosis in HCC.

Dataset Information

Overexpression of modified human TR?1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

Publications

Overexpression of modified human TRβ1 suppresses the growth of hepatocarcinoma SK-hep1 cells in vitro and in xenograft models.

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