scholarly journals MiR-376a and Histone Deacetylation 9 Form A Regulatory Circuitry in Hepatocellular Carcinoma

2015 ◽  
Vol 35 (2) ◽  
pp. 729-739 ◽  
Author(s):  
Yongxia Zheng ◽  
Huan Chen ◽  
Manxiang Yin ◽  
Xiaoqian Ye ◽  
Guiqian Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Deacetylase ◽  
Hdac Inhibitor ◽  
Histone Deacetylation ◽  
Differentially Methylated Region ◽  
Down Regulation ◽  
Acetylation Level ◽  
Histone 3 ◽  
Huh7 Cells ◽  
As Effects

Background/Aims: Our previous study has demonstrated that down-regulation of miR-376a might contribute to the development of hepatocellular carcinoma (HCC), but the mechanism underlying this down-regulation remains obscure. Methods/Results: histone deacetylase (HDAC) inhibitor increased the level of miR-376a in L02 and Huh7 cells by up-regulating the acetylation level of histone 3 at the Maternally expressed 3 (Meg3) differentially methylated region (DMR). Interestingly, HDAC9, a histone deacetylase responsible for deacetylating lysine 18 of histone 3 (H3K18), was identified as the target of miR-376a. In addition, HDAC9 siRNA increased the expression of miR-376a by up-regulating the global histone H3K18 acetylation level, with Meg3 DMR included. Finally, miR-376a and HDAC9 were inversely correlated in HCC. Conclusion: HDAC9 plays an important role both as effects and targets of miR-376a.

scholarly journals MiR-505 suppressed the growth of hepatocellular carcinoma cells via targeting IGF-1R

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Liang Ren ◽  
Yongshan Yao ◽  
Yang Wang ◽  
Shengqiang Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Growth Factor Receptor ◽  
Mechanism Study ◽  
Down Regulation ◽  
Critical Function ◽  
Insulin Growth Factor ◽  
Huh7 Cells ◽  
Hcc Cells

Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers globally. An increasing body of evidence has demonstrated the critical function of microRNAs (miRNAs) in the initiation and progression of human cancers. Here, we showed that miR-505 was down-regulated in HCC tissues and cell lines. Reduced expression of miR-505 was significantly correlated with the worse prognosis of HCC patients. Overexpression of miR-505 suppressed the proliferation, colony formation and induced apoptosis of both HepG2 and Huh7 cells. Further mechanism study uncovered that miR-505 bound the 3′-untranslated region (3′-UTR) of the insulin growth factor receptor (IGF-1R) and inhibited the expression of IGF-1R in HCC cells. The down-regulation of IGF-1R by miR-505 further suppressed the phosphorylation of AKT at the amino acid S473. Consistently, the abundance of glucose transporter (GLUT) 1 (GLUT1) was reduced with the overexpression of miR-505. Down-regulation of GLUT1 by miR-505 consequently attenuated the glucose uptake, lactate production and ATP generation of HCC cells. Collectively, our results demonstrated the tumor suppressive function of miR-505 possibly via inhibiting the glycolysis of HCC cells. These findings suggested miR-505 as an interesting target for designing anti-cancer strategy in HCC.

scholarly journals Anticancer effect of histone deacetylase inhibitor scriptaid as a single agent for hepatocellular carcinoma

2018 ◽  
Vol 38 (4) ◽  
Author(s):  
Linlin Liu ◽  
Xiaoyang Sun ◽  
Yu Xie ◽  
Yinping Zhuang ◽  
Ruosi Yao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Histone Deacetylase ◽  
Transcriptional Activation ◽  
Hdac Inhibitor ◽  
Single Agent ◽  
Disease Recurrence ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Deacetylase Inhibitor ◽  
M Phase

Recurrence is one of the major causes of poor prognosis for patients with hepatocellular carcinoma (HCC), and drug resistance is closely associated with disease recurrence. Histone deacetylase (HDAC) inhibitor scriptaid functions as an anticancer agent in many different types of tumors, but its possible roles in HCC progression have not been explored to date. Herein, we show that HDAC inhibitor scriptaid decreases HCC cell proliferation and induces cell cycle G2/M-phase arrest in a dose-dependent manner. Furthermore, scriptaid triggered HCC cell death via transcriptional activation of p21 and subsequent elevated global H3Ac levels. Importantly, we found that scriptaid showed robust antitumor activity against HCC. Thus, our findings indicate that HDAC inhibitor scriptaid could be an important potential candidate for treatment of HCC patients.

scholarly journals Nrf2 Down-Regulation by Camptothecin Favors Inhibiting Invasion, Metastasis and Angiogenesis in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Qian Liu ◽  
Shanshan Zhao ◽  
Fanguang Meng ◽  
Hankang Wang ◽  
Liwei Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Western Blot ◽  
Mouse Models ◽  
Oxidant Stress ◽  
Invasion And Metastasis ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
Nrf2 Expression

Higher oxidant stress capacity could promote invasion and metastasis. A previous study showed hepatocellular carcinoma (HCC) expressed more Nrf2 than para-carcinoma tissue. The chemotherapeutics such as epirubicin (EPI) could increase Nrf2 expression, while Camptothecin (CPT) could inhibit tumor growth by down-regulating the key molecule of antioxidant stress signal—Nrf2. The role of Nrf2 in invasion and metastasis was still unclear. In this study, we use EPI and CPT to determine the invasion and metastasis in Huh7 cells, H22 and Huh7 mouse models. In Huh7 cells, Nrf2 expression and ROS level were found increased after incubation with EPI by western blot and flow cytometry assay. But with the combination of EPI and CPT, inhibition of Nrf2 could decrease proliferation, invasion, and metastasis, which were investigated by CCK8 assay, wound healing, and Transwell assays. In Huh7 and H22 mouse models, EPI promoted Nrf2 up-regulation and nucleus translocation. Tumor growth was obviously inhibited with a single application of EPI or CPT. The combination of EPI and CPT could inhibit Nrf2 expression but demonstrated more suppressing effect of tumor growth than EPI. Western blot and immunohistochemical staining study revealed that Nrf2 inhibition was beneficial in decreasing the expression of N-cadherin, MMP9, Snail as well as Twist, and increasing E-cadherin, which were associated with epithelial–mesenchymal transition (EMT). Nrf2 down-regulation promoted lung metastasis of H22 cells in vivo. In addition, H&E staining and immunofluorescence staining of VEGFR suggested angiogenesis of Huh7 and H22 tumors was reduced. In conclusion, down-regulation of Nrf2 demonstrated inhibition of invasion, metastasis, and angiogenesis of hepatoma, which may provide a potential therapy in HCC.

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