Research Paper Volume 11, Issue 15 pp 5593—5612

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

Chuanfei Li 1, , Di Zhou 2, , Hao Hong 3, , Shuangyan Yang 4, , Li Zhang 4, , Shiying Li 4, , Peng Hu 4, , Hong Ren 4, , Zhechuan Mei 1, , Hui Tang 4, ,

  • 1 Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
  • 2 Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 4001016, China
  • 3 Department of Orthopaedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
  • 4 Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China

received: May 7, 2019 ; accepted: July 30, 2019 ; published: August 10, 2019 ;

https://doi.org/10.18632/aging.102140
How to Cite

Copyright © 2019 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 TGFβ1 induced EMT model. TGFβ1 mediated EMT could be blocked by miR-140-5p overexpression or FEN1 silencing. Taken together, our findings suggest that FEN1 is regulated by the TGFβ1- miR-140-5p axis and promotes EMT in HCC.

Abbreviations

FEN1: Flap Endonuclease 1; DMEM: Dulbecco’s modified Eagle’s medium; EMT: Epithelial-Mesenchymal Transition; HCC: Hepatocellular Carcinoma.