scholarly journals The Involvement of the ERK-Hypoxia-Angiogenesis Signaling Axis and HIF-1 in Hepatocellular Carcinoma

10.5772/30086 ◽  
2012 ◽  
Author(s):  
Ilias Mylonis ◽  
George Simos
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Axis

Activation of FXR modulates SOCS3/Jak2/STAT3 signaling axis in a NASH-dependent hepatocellular carcinoma animal model

2021 ◽  
pp. 114497
Author(s):  
Yasmeen M Attia ◽  
Rasha A Tawfiq ◽  
Abdullah A Gibriel ◽  
Aya A Ali ◽  
Dina H Kassem ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Animal Model ◽  
Stat3 Signaling ◽  
Signaling Axis

scholarly journals CircSOD2 induced epigenetic alteration drives hepatocellular carcinoma progression through activating JAK2/STAT3 signaling pathway

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Zhongwei Zhao ◽  
Jingjing Song ◽  
Bufu Tang ◽  
Shiji Fang ◽  
Dengke Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Migration ◽  
Real Time ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Signaling Axis

Abstract Background Emerging evidence suggests that circular RNAs play critical roles in disease development especially in cancers. Previous genome-wide RNA-seq studies found that a circular RNA derived from SOD2 gene was highly upregulated in hepatocellular carcinoma (HCC), however, the role of circSOD2 in HCC remains largely unknown. Methods The expression profiling of circSOD2 and microRNA in HCC patients were assessed by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). SiRNA or CRISPR-CAS9 were used to silence gene expression. The biological function of circSOD2 in HCC was investigated using in vitro and in vivo studies including, trans-well cell migration, cell apoptosis, cell cycle, CCK8, siRNA interference, western blots, and xenograft mouse model. The underlying molecular mechanism was determined by Chromatin Immunoprecipitation quantitative real time PCR (ChIP-qPCR), bioinformatic analysis, biotin-pull down, RNA immunoprecipitation, 5-mc DNA pulldown and luciferase assays. Results In accordance with previous sequencing results, here, we demonstrated that circSOD2 was highly expressed in HCC tumor tissues compared with normal liver tissues. Mechanically, we showed that histone writer EP300 and WDR5 bind to circSOD2 promoter and trigger its promoter H3K27ac and H3K4me3 modification, respectively, which further activates circSOD2 expression. SiRNA mediated circSOD2 suppression impaired liver cancer cell growth, cell migration, prohibited cell cycle progression and in vivo tumor growth. By acting as a sponge, circSOD2 inhibits miR-502-5p expression and rescues miR-502-5p target gene DNMT3a expression. As a DNA methyltransferase, upregulated DNMA3a suppresses SOCS3 expression by increasing SOCS3 promoter DNA methylation. This event further accelerates SOCS3 downstream JAK2/STAT3 signaling pathway activation. In addition, we also found that activated STAT3 regulates circSOD2 expression in a feedback way. Conclusion The novel signaling axis circSOD2/miR-502-5p/DNMT3a/JAK2/STAT3/circSOD2 provides a better understanding of HCC tumorigenesis. The molecular mechanism underlying this signaling axis offers new prevention and treatment of HCC.

scholarly journals MicroRNA-29a induces loss of 5-hydroxymethylcytosine and promotes metastasis of hepatocellular carcinoma through a TET–SOCS1–MMP9 signaling axis

2017 ◽  
Vol 8 (6) ◽  
pp. e2906-e2906 ◽  
Author(s):  
Qing Chen ◽  
Dan Yin ◽  
Yong Zhang ◽  
Lei Yu ◽  
Xue-Dong Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Axis

scholarly journals Long non-coding RNA00364 represses hepatocellular carcinoma cell proliferation via modulating p-STAT3-IFIT2 signaling axis

Oncotarget ◽  
2017 ◽  
Vol 8 (60) ◽  
pp. 102006-102019 ◽  
Author(s):  
Wei-Guo Tang ◽  
Bo Hu ◽  
Hai-Xiang Sun ◽  
Qi-Man Sun ◽  
Chao Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Carcinoma Cell ◽  
Signaling Axis ◽  
Hepatocellular Carcinoma Cell

scholarly journals Green Tea-Derived Theabrownin Induces Cellular Senescence and Apoptosis of Hepatocellular Carcinoma via P53 Signaling-Mediated Mechanism Bypassed by JNK Regulation

2021 ◽  
Author(s):  
Jiaan Xu ◽  
Bo Yan ◽  
Xiujuan Xiao ◽  
Qiang Yuan ◽  
Xiaoqiao Dong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Xenograft Model ◽  
Dependent Manner ◽  
Dapi Staining ◽  
P53 Signaling ◽  
Animal Data ◽  
Huh7 Cells ◽  
Signaling Axis ◽  
Underlying Mechanisms ◽  
Hcc Cells

Abstract Background: Theabrownin (TB) is a bioactive component of tea and has been reported to exert effects against many human cancers, but its efficacy and mechanism on hepatocellular carcinoma (HCC) with different p53 genotypes remains unclarified. Methods: MTT assay, DAPI staining, flow cytometry and SA-β-gal staining were applied to evaluate the effects of TB on HCC cells. Quantitative real time PCR (qPCR) and Western blot (WB) were conducted to explore the molecular mechanism of TB. And xenograft model of zebrafish was established to evaluate the anti-tumor effect of TB.Results: MTT assays showed that TB significantly inhibited the proliferation of SK-Hep-1, HepG2, and Huh7 cells in a dose-dependent manner, of which SK-Hep-1 was the most sensitive one with the lowest IC50 values. The animal data showed that TB remarkably suppressed SK-Hep-1 tumor growth in xenograft model of zebrafish. The cellular data showed TB′s pro-apoptotic and pro-senescent effect on SK-Hep-1 cells. The molecular results revealed the mechanism of TB that p53 signaling pathway (p-ATM, p-ATR, γ-H2AX, p-Chk2, and p-p53) was activated with up-regulation of downstream senescent genes (P16, P21, IL-6 and IL-8) as well as apoptotic genes (Bim, Bax and PUMA) and proteins (Bax, c-Casp9 and c-PARP). The p53-mediated mechanism was verified by using p53-siRNA. Moreover, by using JNK-siRNA, we found JNK as a bypass regulator in TB′s mechanism. Conclusions: To sum up, TB exerted tumor-inhibitory, pro-senescent and pro-apoptotic effects on SK-Hep-1 cells through ATM-Chk2-p53 signaling axis in accompany with JNK bypass regulation. This is the first report on the pro-senescent effect and multi-target (p53 and JNK) mechanism of TB on HCC cells, providing new insights into the underlying mechanisms of TB′s anti-HCC efficacy.

Ssu72-HNF4α signaling axis classify the transition from steatohepatitis to hepatocellular carcinoma

2021 ◽  
Author(s):  
Hyun-Soo Kim ◽  
Joon-Sup Yoon ◽  
Yoon Jeon ◽  
Eun-Ji Park ◽  
Jin-Kwan Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Axis
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