scholarly journals Analysis of hypoxia inducible factor 1 alpha subunit (HIF1A)- and endothelial PAS domain protein 1 (EPAS1)-dependent transcriptomes in human HepG2 hepatocellular carcinoma cells

2019 ◽  
Author(s):  
T Geis
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hypoxia Inducible Factor ◽  
Carcinoma Cells ◽  
Alpha Subunit ◽  
Pas Domain ◽  
Hepatocellular Carcinoma Cells ◽  
Hypoxia Inducible Factor 1 ◽  
Domain Protein

scholarly journals Houttuynia cordata Thunb Promotes Activation of HIF-1A–FOXO3 and MEF2A Pathways to Induce Apoptosis in Human HepG2 Hepatocellular Carcinoma Cells

2016 ◽  
Vol 16 (3) ◽  
pp. 360-372 ◽  
Author(s):  
Jung Min Kim ◽  
In-Hu Hwang ◽  
Ik-Soon Jang ◽  
Min Kim ◽  
In Seok Bang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Hypoxia Inducible Factor ◽  
Carcinoma Cells ◽  
Houttuynia Cordata ◽  
Hepatocellular Carcinoma Cells ◽  
Human Liver Cancer ◽  
Houttuynia Cordata Thunb ◽  
Human Liver Cancer Cells

Houttuynia cordata Thunb ( H cordata), a medicinal plant, has anticancer activity, as it inhibits cell growth and induces cell apoptosis in cancer. However, the potential anti-cancer activity and mechanism of H cordata for human liver cancer cells is not well understood. Recently, we identified hypoxia-inducible factor (HIF)-1A, Forkhead box (FOX)O3, and MEF2A as proapoptotic factors induced by H cordata, suggesting that HIF-1A, FOXO3, and MEF2A contribute to the apoptosis of HepG2 hepatocellular carcinoma cells. FOXO3 transcription factors regulate target genes involved in apoptosis. H cordata significantly increased the mRNA and protein expression of HIF-1A and FOXO3 and stimulated MEF2A expression in addition to increased apoptosis in HepG2 cells within 24 hours. Therefore, we determined the potential role of FOXO3 on apoptosis and on H cordata–induced MEF2A in HepG2 cells. HIF-1A silencing by siRNA attenuated MEF2A and H cordata–mediated FOXO3 upregulation in HepG2 cells. Furthermore, H cordata–mediated MEF2A expression enhanced caspase-3 and caspase-7, which were abolished on silencing FOXO3 with siRNA. In addition, H cordata inhibited growth of human hepatocellular carcinoma xenografts in nude mice. Taken together, our results demonstrate that H cordata enhances HIF-1A/FOXO3 signaling, leading to MEF2A upregulation in HepG2 cells, and in parallel, it disturbs the expression of Bcl-2 family proteins (Bax, Bcl-2, and Bcl-xL), which results in apoptosis. Taken together, these findings demonstrate that H cordata promotes the activation of HIF-1A–FOXO3 and MEF2A pathways to induce apoptosis in human HepG2 hepatocellular carcinoma cells and is, therefore, a promising candidate for antitumor drug development.

scholarly journals Lack of MOF Decreases Susceptibility to Hypoxia and Promotes Multidrug Resistance in Hepatocellular Carcinoma via HIF-1α

2021 ◽  
Vol 9 ◽  
Author(s):  
Meng Wang ◽  
Haoyu Liu ◽  
Xu Zhang ◽  
Wenbo Zhao ◽  
Xiaoyan Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mrna Expression ◽  
Trichostatin A ◽  
Hypoxia Inducible Factor ◽  
Carcinoma Cells ◽  
Hypoxia Tolerance ◽  
Hepatocellular Carcinoma Cells ◽  
Carcinoma Cell Lines ◽  
Downstream Effects ◽  
Functional Inactivation

Hypoxia-inducible factor-1α (HIF-1α) promotes oncogenesis in hepatocellular carcinoma and is functionally linked to cell proliferation, chemoresistance, metastasis and angiogenesis. It has been confirmed that the low expression level of Males absent on the first (MOF) in hepatocellular carcinoma leads to poor prognosis of patients. However, potential regulatory mechanisms of MOF in response to hypoxia remain elusive. Our results demonstrate that MOF expression is negatively associated with HIF-1α expression in hepatocellular carcinoma tissues and in response to chloride-mimicked hypoxia in hepatocellular carcinoma cell lines. MOF regulates HIF-1α mRNA expression and also directly binds to HIF-1α to mediate HIF-1α N-terminal lysine acetylation, ubiquitination and degradation, with downstream effects on MDR1 levels. Functional inactivation of MOF enhances HIF-1α stability and causes cell tolerance to hypoxia that is insensitive to histone deacetylase inhibitor treatment. Dysfunction of MOF in hepatocellular carcinoma cells also results in chemoresistance to trichostatin A, sorafenib and 5-fluorouracil via HIF-1α. Our results suggest that MOF regulates hypoxia tolerance and drug resistance in hepatocellular carcinoma cells by modulating both HIF-1α mRNA expression and N-terminal acetylation of HIF-1α, providing molecular insight into MOF-dependent oncogenic function of hepatocellular carcinoma cells.

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