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FGG promotes migration and invasion in hepatocellular carcinoma cells through activating epithelial to mesenchymal transition

Authors Zhang X, Wang F, Huang Y, Ke K, Zhao B, Chen L, Liao N, Wang L, Li Q, Liu X, Wang Y, Liu J

Received 20 September 2018

Accepted for publication 20 December 2018

Published 19 February 2019 Volume 2019:11 Pages 1653—1665

DOI https://doi.org/10.2147/CMAR.S188248

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Dr Antonella D'Anneo


Xiang Zhang,1–3 Fei Wang,2,3 Yanbing Huang,1–3 Kun Ke,1–3 Bixing Zhao,2,3 Lihong Chen,4 Naishun Liao,2,3 Lei Wang,2,3 Qin Li,5 Xiaolong Liu,2,3 Yingchao Wang,2,3 Jingfeng Liu1–3,6

1The First Affiliated Hospital of Fujian Medical University, Fuzhou, China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; 3The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, China; 4Department of Pathology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; 5Department of Infectious Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China; 6Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China

Purpose: The aim of this work was to investigate the clinicopathological significance of fibrinogen gamma chain (FGG) and its biological roles during hepatocellular carcinoma (HCC) development and progression.
Methods: The expression of FGG was examined by Western blot and reverse transcription quantitative PCR in two different sample sets, including 24 or 35 pairs of HCC tumor tissues and their corresponding adjacent non-tumorous tissues. Afterward, association analysis between the expression of FGG and clinicopathological characteristics was systematically analyzed in 79 HCC patients. Subsequently, the mobility and invasiveness of SK-HEP-1 cells with FGG overexpression or knockdown were evaluated by transwell assay and wound healing assay. Additionally, the expressions of epithelial to mesenchymal transition (EMT)-associated markers were also detected in FGG overexpressed or silenced SK-HEP-1 cells.
Results: The expression of FGG was significantly increased in primary HCC tissues comparing with its corresponding adjacent non-tumorous tissues. Clinical pathological analysis demonstrated that upregulation of intracellular FGG was significantly associated with increased vascular invasion, more satellite nodules, and more advanced TNM stage, and HCC patients with stronger expression of FGG had a higher recurrence rate and correspondingly a shorter overall survival time. Meanwhile, the high expression of FGG was also proved to be an independent risk factor for disease-free survival after surgical resection. In vitro phenotype studies showed that overexpression of FGG could promote the migration and invasion in SK-HEP-1 cells; conversely, these phenotypes could be significantly inhibited by knocking down the expression of FGG. Mechanism studies indicated that FGG could promote the migration and invasion through EMT signaling pathway by regulating the expressions of Slug and ZEB1.
Conclusion: FGG played important roles in enhancing cancer cell motility and invasiveness through EMT signaling, and might serve as a potential prognostic biomarker for HCC patients.

Keywords: hepatocellular carcinoma, fibrinogen gamma chain, epithelial to mesenchymal transition, recurrence, metastasis


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