Longer warm ischemia can accelerate tumor growth through the induction of HIF-1α and the IL-6-JAK-STAT3 signaling pathway in a rat hepatocellular carcinoma model

2016 ◽  
Vol 23 (12) ◽  
pp. 771-779 ◽  
Author(s):  
Yuhei Hamaguchi ◽  
Akira Mori ◽  
Yasuhiro Fujimoto ◽  
Takashi Ito ◽  
Taku Iida ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Signaling Pathway ◽  
Warm Ischemia ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

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 3-Formylchromone Counteracts STAT3 Signaling Pathway by Elevating SHP-2 Expression in Hepatocellular Carcinoma

Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 29
Author(s):  
Chakrabhavi Dhananjaya Mohan ◽  
Min Hee Yang ◽  
Shobith Rangappa ◽  
Arunachalam Chinnathambi ◽  
Sulaiman Ali Alharbi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Tyrosine Kinases ◽  
Present Report ◽  
Migration And Invasion ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Substantial Toxicity ◽  
Transcription 3 ◽  
Constitutive Phosphorylation

Hepatocellular carcinoma (HCC) is one of the leading cancers that contribute to a large number of deaths throughout the globe. The signal transducer and activator of transcription 3 (STAT3) is a tumorigenic protein that is overactivated in several human malignancies including HCC. In the present report, the effect of 3-formylchromone (3FC) on the STAT3 signaling pathway in the HCC model was investigated. 3FC downregulated the constitutive phosphorylation of STAT3 and non-receptor tyrosine kinases such as JAK1 and JAK2. It also suppressed the transportation of STAT3 to the nucleus and reduced its DNA-binding ability. Pervanadate treatment overrode the 3FC-triggered STAT3 inhibition, and the profiling of cellular phosphatase expression revealed an increase in SHP-2 levels upon 3FC treatment. The siRNA-driven deletion of SHP-2 led to reinstate STAT3 activation. 3FC downmodulated the levels of various oncogenic proteins and decreased CXCL12-driven cell migration and invasion. Interestingly, 3FC did not exhibit any substantial toxicity, whereas it significantly regressed tumor growth in an orthotopic HCC mouse model and abrogated lung metastasis. Overall, 3FC can function as a potent agent that can display antitumor activity by targeting STAT3 signaling in HCC models.

scholarly journals Physagulide Q suppresses proliferation and induces apoptosis in human hepatocellular carcinoma cells by regulating the ROS-JAK2/Src-STAT3 signaling pathway

RSC Advances ◽  
2017 ◽  
Vol 7 (21) ◽  
pp. 12793-12804 ◽  
Author(s):  
Yan-Wei Yang ◽  
Lei Yang ◽  
Chao Zhang ◽  
Cai-Yun Gao ◽  
Ting Ma ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Natural Compound ◽  
Carcinoma Cells ◽  
Human Hepatocellular Carcinoma ◽  
Hepatocellular Carcinoma Cells ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Physalis Angulata ◽  
Human Hepatocellular Carcinoma Cells

Physagulide Q (PQ), a new natural compound, was isolated from Physalis angulata L. in our laboratory.

scholarly journals Peri-tumor fibroblasts promote tumorigenesis and metastasis of hepatocellular carcinoma via Interleukin6/STAT3 signaling pathway

2019 ◽  
Vol Volume 11 ◽  
pp. 2889-2901 ◽  
Author(s):  
Zhenxiong Zhao ◽  
Si Xiong ◽  
Ronghua Wang ◽  
Yawen Li ◽  
Xiju Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

Pyrimidine-2,4-dione Targets STAT3 Signaling Pathway to Induce Cytotoxicity in Hepatocellular Carcinoma Cells

2021 ◽  
pp. 128332
Author(s):  
Ayyiliath M Sajith ◽  
Kereyagalahally H. Narasimhamurthy ◽  
Muthu K. Shanmugam ◽  
Shobith Rangappa ◽  
S. Chandra Nayak ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Vicenin-2 is a novel inhibitor of STAT3 signaling pathway in human hepatocellular carcinoma

2020 ◽  
Vol 69 ◽  
pp. 103921 ◽  
Author(s):  
Gengzhen Huang ◽  
Shiqing Li ◽  
Yaodan Zhang ◽  
Xiaoqing Zhou ◽  
Wei Chen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Human Hepatocellular Carcinoma ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

scholarly journals Niclosamide Inhibits Cell Growth and Enhances Drug Sensitivity of Hepatocellular Carcinoma Cells via STAT3 Signaling Pathway

2018 ◽  
Vol 9 (22) ◽  
pp. 4150-4155 ◽  
Author(s):  
Chengzhi Wang ◽  
Xiaoqing Zhou ◽  
Hongjuan Xu ◽  
Xiaqing Shi ◽  
Jinfeng Zhao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Drug Sensitivity ◽  
Carcinoma Cells ◽  
Hepatocellular Carcinoma Cells ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway

LINC00346 promotes hepatocellular carcinoma progression via activating the JAK‐STAT3 signaling pathway

2019 ◽  
Vol 121 (1) ◽  
pp. 735-742 ◽  
Author(s):  
Yun‐Zhi Yin ◽  
Wei‐Hua Zheng ◽  
Xin Zhang ◽  
Yan‐Hao Chen ◽  
Yan‐Hong Tuo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway
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