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25-HC promotes hepatocellular carcinoma metastasis through up-regulation of TLR4 dependent FABP4.


ABSTRACT: Metabolic syndrome is a significant risk factor for the development of hepatocellular carcinoma (HCC). 25-HC (25-hydroxycholesterol) synthesized from cholesterol plays an important role in lipid metabolism. However, the functions and mechanism of 25-HC in HCC remain largely unknown. In this study, we demonstrated that 25-HC promoted HCC cells migration and intrahepatic and extrahepatic metastasis while did not affect the cells proliferation and apoptosis. Mechanistically, the promotive effect of 25-HC was through up-regulation of Toll-like receptor 4 (TLR4) dependent fatty acid binding protein 4 (FABP4). Inhibition of FABP4 hindered 25-HC-induced cells migration and metastasis. Moreover, up-regulation of FABP4 was observed in HCC tissues from database analysis. In summary, our study reveals the effects and mechanism of 25-HC/TLR4/FABP4 axis in promoting HCC metastasis, which provides novel avenue for therapeutic intervention against HCC progression.

SUBMITTER: Wang S 

PROVIDER: S-EPMC6834473 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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25-HC promotes hepatocellular carcinoma metastasis through up-regulation of TLR4 dependent FABP4.

Wang Saisai S   Yao Yuanyuan Y   Wang Xiao X   Zheng Gang G   Ouyang Wei W   Chen Wenbin W  

American journal of cancer research 20191001 10


Metabolic syndrome is a significant risk factor for the development of hepatocellular carcinoma (HCC). 25-HC (25-hydroxycholesterol) synthesized from cholesterol plays an important role in lipid metabolism. However, the functions and mechanism of 25-HC in HCC remain largely unknown. In this study, we demonstrated that 25-HC promoted HCC cells migration and intrahepatic and extrahepatic metastasis while did not affect the cells proliferation and apoptosis. Mechanistically, the promotive effect of  ...[more]

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