Far Upstream Element-Binding Protein 1 Facilitates Hepatocellular Carcinoma Invasion and Metastasis

2018 ◽  
Author(s):  
Pei-Yao Fu ◽  
Bo Hu ◽  
Xiao-Lu Ma ◽  
Wei-Guo Tang ◽  
Zhang-Fu Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Binding Protein ◽  
Invasion And Metastasis ◽  
Element Binding Protein ◽  
Upstream Element

MicroRNA-591 Functions as a Tumor Suppressor in Hepatocellular Carcinoma by Lowering Drug Resistance through Inhibition of Far-Upstream Element-Binding Protein 2-Mediated Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin Axis

Pharmacology ◽  
2019 ◽  
Vol 104 (3-4) ◽  
pp. 173-186 ◽  
Author(s):  
Huili Wang ◽  
Yanhua Tang ◽  
Dong Yang ◽  
Linjing Zheng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Binding Protein ◽  
Mammalian Target Of Rapamycin ◽  
Target Of Rapamycin ◽  
Luciferase Reporter ◽  
Gene Assay ◽  
Element Binding Protein ◽  
Upstream Element ◽  
Phosphoinositide 3 Kinase

MicroRNAs, a group of noncoding regulatory RNAs, are involved in oncogenesis, cell survival, and chemosensitivity. First, microarray-based analysis predicted that far-upstream element-binding protein 2 (FBP2) was upregulated in hepatocellular carcinoma (HCC), which may be regulated by miR-591. In this study, we hypothesize an inhibitory role of miR-591 in HCC via regulating FBP2. Next, reverse transcription quantitative polymerase chain reaction found that FBP2 expressed highly and miR-591 expresses poorly in HCC tissues. Then, the negative correlation between miR-591 and mRNA expression of FBP2 was identified by Pearson’s correlation coefficient, and putative miR-591-binding sites on the 3′-untranslated region of FBP2 was validated using a dual-luciferase reporter gene assay. After the expression of miR-591 and FBP2 was altered in the drug-resistant CD133+/CD44+ cells, a series of in vitro and in vivo experiments demonstrated that either miR-591 overexpression or FBP2 silencing inhibited the abilities of sphere formation and colony formation, drug resistance, as well as tumorigenicity. It was further observed that miR-591 could suppress FBP2 expression by blocking the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin axis. Above results highlighted an inhibitory effect of miR-591 on the development of HCC by reducing the drug resistance of HCC stem cells. It revealed miR-591 as a new target in the treatment of HCC.

scholarly journals Overexpression of the far upstream element binding protein 1 in hepatocellular carcinoma is required for tumor growth

Hepatology ◽  
2009 ◽  
Vol 50 (4) ◽  
pp. 1121-1129 ◽  
Author(s):  
Uta Rabenhorst ◽  
Rasa Beinoraviciute-Kellner ◽  
Marie-Luise Brezniceanu ◽  
Stefan Joos ◽  
Frauke Devens ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Growth ◽  
Binding Protein ◽  
Element Binding Protein ◽  
Upstream Element

scholarly journals Far upstream element-binding protein 1 facilitates hepatocellular carcinoma invasion and metastasis

2019 ◽  
Vol 41 (7) ◽  
pp. 950-960 ◽  
Author(s):  
Pei-Yao Fu ◽  
Bo Hu ◽  
Xiao-Lu Ma ◽  
Wei-Guo Tang ◽  
Zhang-Fu Yang ◽  
...  
Keyword(s):  
Binding Protein ◽  
Invasion And Metastasis ◽  
Smad Pathway ◽  
Mesenchymal Transition ◽  
Thrombospondin 1 ◽  
Element Binding Protein ◽  
Upstream Element

Abstract Previous research suggests that far upstream element-binding protein 1 (FUBP1) plays an important role in various tumors including epatocellular carcinoma (HCC). However, the role of FUBP1 in liver cancer remains controversial, and the regulatory pathway by FUBP1 awaits to be determined. This study aims to identify the role of FUBP1 in HCC progression. Our result shows that the high level of FUBP1 expression in HCC predicts poor prognosis after surgery. Overexpression of FUBP1 promotes HCC proliferation, invasion, and metastasis by activating transforming growth factor-β (TGF-β)/Smad pathway and enhancing epithelial-mesenchymal transition (EMT) in vitro and in vivo. Inhibitor of Thrombospondin-1 (LSKL) could inhibit HCC proliferation and invasion in vitro and in vivo by blocking the activation of TGF-β/Smad pathway mediated by thrombospondin-1 (THBS1). Our study identified the critical role of FUBP1-THBS1-TGF-β signaling axis in HCC and provides potentially new therapeutic modalities in HCC.

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