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TGF?1- miR-140-5p axis mediated up-regulation of Flap Endonuclease 1 promotes epithelial-mesenchymal transition in hepatocellular carcinoma.


ABSTRACT: Flap Endonuclease 1 (FEN1) is a known oncogene in an array of cancers, but its role in hepatocellular carcinoma (HCC) remains obscure. In this study, we report that FEN1 expression was elevated in the Cancer Genome Atlas (TCGA) database which was verified in HCC tissue and hepatoma cell lines. Pearson correlation analysis indicated that FEN1 was involved in HCC metastasis. We demonstrated that FEN1 silencing inhibits HCC cell epithelial-mesenchymal transition (EMT), invasion and migration in vitro and significantly suppressed tumor growth and metastasis in vivo. Conversely, FEN1 overexpression in HCC cells enhanced these metastatic processes. We further confirmed that FEN1 was a direct target of miR-140-5p, which was down-regulated in HCC tissues, and negatively correlated with FEN1 expression. Moreover, low miR-140-5p levels and high FEN1 expression predicted a poor clinical outcome. The effects of FEN1 overexpression could be partially abolished by miR-140-5p. miR-140-5p down-regulation and FEN1 overexpression were observed in a TGF?1 induced EMT model. TGF?1 mediated EMT could be blocked by miR-140-5p overexpression or FEN1 silencing. Taken together, our findings suggest that FEN1 is regulated by the TGF?1- miR-140-5p axis and promotes EMT in HCC.

SUBMITTER: Li C 

PROVIDER: S-EPMC6710057 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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TGFβ1- miR-140-5p axis mediated up-regulation of Flap Endonuclease 1 promotes epithelial-mesenchymal transition in hepatocellular carcinoma.

Li Chuanfei C   Zhou Di D   Hong Hao H   Yang Shuangyan S   Zhang Li L   Li Shiying S   Hu Peng P   Ren Hong H   Mei Zhechuan Z   Tang Hui H  

Aging 20190810 15


Flap Endonuclease 1 (FEN1) is a known oncogene in an array of cancers, but its role in hepatocellular carcinoma (HCC) remains obscure. In this study, we report that FEN1 expression was elevated in the Cancer Genome Atlas (TCGA) database which was verified in HCC tissue and hepatoma cell lines. Pearson correlation analysis indicated that FEN1 was involved in HCC metastasis. We demonstrated that FEN1 silencing inhibits HCC cell epithelial-mesenchymal transition (EMT), invasion and migration <i>in  ...[more]

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