Functional Switching of TGF-β1 Signaling in Liver Cancer via Epigenetic Modulation of a Single CpG Site in TTP Promoter

2010 ◽  
Vol 138 (5) ◽  
pp. 1898-1908.e12 ◽  
Author(s):  
Bo Hwa Sohn ◽  
In Young Park ◽  
Jung Ju Lee ◽  
Suk–Jin Yang ◽  
Ye Jin Jang ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cpg Site ◽  
Functional Switching ◽  
Epigenetic Modulation ◽  
Tgf Β1

scholarly journals Echinacoside exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wen Li ◽  
Jing Zhou ◽  
Yajie Zhang ◽  
Jing Zhang ◽  
Xue Li ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
Luciferase Reporter ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Expression Levels ◽  
Liver Cancer Cells ◽  
Anti Tumor Activity ◽  
Tgf Β1

Abstract Background Echinacoside (ECH) is the main active ingredient of Cistanches Herba, which is known to have therapeutic effects on metastatic tumors. However, the effects of ECH on liver cancer are still unclear. This study was to investigate the effects of ECH on the aggression of liver cancer cells. Methods Two types of liver cancer cells Huh7 and HepG2 were treated with different doses of ECH at different times and gradients. MTT and colony formation assays were used to determine the effects of ECH on the viability of Huh7 and HepG2 cells. Transwell assays and flow cytometry assays were used to detect the effects of ECH treatment on the invasion, migration, apoptosis and cell cycle of Huh7 and HepG2 cells. Western blot analysis was used to detect the effects of ECH on the expression levels of TGF-β1, smad3, smad7, apoptosis-related proteins (Caspase-3, Caspase-8), and Cyto C in liver cancer cells. The relationship between miR-503-3p and TGF-β1 was detected using bioinformatics analysis and Luciferase reporter assay. Results The results showed that ECH inhibited the proliferation, invasion and migration of Huh7 and HepG2 cells in a dose- and time-dependent manner. Moreover, we found that ECH caused Huh7 and HepG2 cell apoptosis by blocking cells in S phase. Furthermore, the expression of miR-503-3p was found to be reduced in liver tumor tissues, but ECH treatment increased the expression of miR-503-3p in Huh7 and HepG2 cells. In addition, we found that TGF-β1 was identified as a potential target of miR-503-3p. ECH promoted the activation of the TGF-β1/Smad signaling pathway and increased the expression levels of Bax/Bcl-2. Moreover, ECH could trigger the release of mitochondrial Cyto C, and cause the reaction Caspases grade. Conclusions This study demonstrates that ECH exerts anti-tumor activity via the miR-503-3p/TGF-β1/Smad aixs in liver cancer, and provides a safe and effective anti-tumor agent for liver cancer.

scholarly journals Effects of Pyrrole-Imidazole Polyamides Targeting Human TGF-β1 on the Malignant Phenotypes of Liver Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2883 ◽  
Author(s):  
Keiko Takagi ◽  
Yutaka Midorikawa ◽  
Tadatoshi Takayama ◽  
Hayato Abe ◽  
Kyoko Fujiwara ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Expression Level ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Liver Cancer Cells ◽  
Tgf Β1

Synthetic pyrrole-imidazole (PI) polyamides bind to the minor groove of double-helical DNA with high affinity and specificity, and inhibit the transcription of corresponding genes. In liver cancer, transforming growth factor (TGF)-β expression is correlated with tumor grade, and high-grade liver cancer tissues express epithelial-mesenchymal transition markers. TGF-β1 was reported to be involved in cancer development by transforming precancer cells to cancer stem cells (CSCs). This study aimed to evaluate the effects of TGF-β1-targeting PI polyamide on the growth of liver cancer cells and CSCs and their TGF-β1 expression. We analyzed TGF-β1 expression level after the administration of GB1101, a PI polyamide that targets human TGF-β1 promoter, and examined its effects on cell proliferation, invasiveness, and TGF-β1 mRNA expression level. GB1101 treatment dose-dependently decreased TGF-β1 mRNA levels in HepG2 and HLF cells, and inhibited HepG2 colony formation associated with downregulation of TGF-β1 mRNA. Although GB1101 did not substantially inhibit the proliferation of HepG2 cells compared to untreated control cells, GB1101 significantly suppressed the invasion of HLF cells, which displayed high expression of CD44, a marker for CSCs. Furthermore, GB1101 significantly inhibited HLF cell sphere formation by inhibiting TGF-β1 expression, in addition to suppressing the proliferation of HLE and HLF cells. Taken together, GB1101 reduced TGF-β1 expression in liver cancer cells and suppressed cell invasion; therefore, GB1101 is a novel candidate drug for the treatment of liver cancer.

scholarly journals Long non‑coding RNA snaR is involved in the metastasis of liver cancer possibly through TGF‑β1

2019 ◽  
Author(s):  
Zhitian Shi ◽  
Dong Wei ◽  
Huamei Wu ◽  
Jiayun Ge ◽  
Xuefen Lei ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Non Coding Rna ◽  
Long Non Coding Rna ◽  
Tgf Β1

Abstract 4252: Mechanistic and clinical implications of epigenetic modulation in liver cancer stem cells

2010 ◽  
Author(s):  
Jens U. Marquardt ◽  
Chiara Raggi ◽  
Jesper B. Andersen ◽  
Deakwan Seo ◽  
Itzhak Avital ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Clinical Implications ◽  
Liver Cancer Stem Cells ◽  
Epigenetic Modulation

scholarly journals TGF-β1 accelerates the hepatitis B virus X-induced malignant transformation of hepatic progenitor cells by upregulating miR-199a-3p

Oncogene ◽  
2019 ◽  
Vol 39 (8) ◽  
pp. 1807-1820 ◽  
Author(s):  
Ke-shuai Dong ◽  
Yan Chen ◽  
Guang Yang ◽  
Zhi-bin Liao ◽  
Hong-wei Zhang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Progenitor Cells ◽  
Malignant Transformation ◽  
Transforming Growth Factor ◽  
Hepatic Progenitor Cells ◽  
B Virus ◽  
Mesenchymal Transformation ◽  
Tgf Β1

AbstractIncreasing evidence has suggested that liver cancer arises partially from transformed hepatic progenitor cells (HPCs). However, the detailed mechanisms underlying HPC transformation are poorly understood. In this study, we provide evidence linking the coexistence of hepatitis B virus X protein (HBx) and transforming growth factor beta 1 (TGF-β1) with miR-199a-3p in the malignant transformation of HPCs. The examination of liver cancer specimens demonstrated that HBx and TGF-β1 expression was positively correlated with epithelial cell adhesion molecule (EpCAM) and cluster of differentiation 90 (CD90). Importantly, EpCAM and CD90 expression was much higher in the specimens expressing both high HBx and high TGF-β1 than in those with high HBx or high TGF-β1 and the double-low-expression group. HBx and TGF-β1 double-high expression was significantly associated with poor prognosis in primary liver cancer. We also found that HBx and TGF-β1 induced the transformation of HPCs into hepatic cancer stem cells and promoted epithelial–mesenchymal transformation, which was further enhanced by concomitant HBx and TGF-β1 exposure. Moreover, activation of the c-Jun N-terminal kinase (JNK)/c-Jun pathway was involved in the malignant transformation of HPCs. miR-199a-3p was identified as a significantly upregulated microRNA in HPCs upon HBx and TGF-β1 exposure, which were shown to promote miR-199a-3p expression via c-Jun-mediated activation. Finally, we found that miR-199a-3p was responsible for the malignant transformation of HPCs. In conclusion, our results provide evidence that TGF-β1 cooperates with HBx to promote the malignant transformation of HPCs through a JNK/c-Jun/miR-199a-3p-dependent pathway. This may open new avenues for therapeutic interventions targeting the malignant transformation of HPCs in treating liver cancer.

scholarly journals TGF-β1 polymorphisms and familial aggregation of liver cancer in Guangxi, China

2015 ◽  
Vol 14 (3) ◽  
pp. 8147-8160 ◽  
Author(s):  
P.Q. Wan ◽  
J.Z. Wu ◽  
L.Y. Huang ◽  
J.L. Wu ◽  
Y.H. Wei ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Familial Aggregation ◽  
Tgf Β1

scholarly journals Ailanthoidol, a Neolignan, Suppresses TGF-β1-Induced HepG2 Hepatoblastoma Cell Progression

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1110
Author(s):  
Tsui-Hwa Tseng ◽  
Huei-Jane Lee ◽  
Yean-Jang Lee ◽  
Ko-Chao Lee ◽  
Chien-Heng Shen ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Mouse Skin ◽  
Transforming Growth Factor Β1 ◽  
Mitogen Activated Protein Kinase ◽  
Matrix Metalloproteinase 2 ◽  
Migration And Invasion ◽  
Induced Expression ◽  
Tgf Β1

Ailanthoidol (ATD), a neolignan, possessed an antitumor promotion effect in the mouse skin model in our previous investigation. However, other antitumor properties remain to be elucidated. Liver cancer is a major cause of death in the world, and its prognosis and survival rate are poor. Therefore, the prevention and therapy of liver cancer have received much attention. TGF (transforming growth factor)-β1, a cytokine, plays a critical role in the progression of liver cancer. This study determined the inhibitory effects of ATD on the migration and invasion induced by TGF-β1 in HepG2 hepatoblastoma cells. Furthermore, ATD reduced the TGF-β1-promoted colony number of HepG2 hepatoblastoma cells. In addition to reversing TGF-β1-induced cell scattering, ATD suppressed TGF-β1-induced expression of integrin α3, vimentin, N-cadherin, and matrix metalloproteinase 2 (MMP2). Finally, this study found that ATD significantly inhibited TGF-β1-promoted phosphorylation of p-38 mitogen-activated protein kinase (MAPK) and Smad 2. Furthermore, the administration of SB203580 (p38MAPK inhibitor) suppressed TGF-β1-induced expression of integrin α3, N-cadherin, and MMP2. These results demonstrate a novel mechanism of ATD against progression of liver cancer.

Sign in / Sign up

Export Citation Format

Share Document