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Research Paper|Volume 11, Issue 17|pp 6674—6690

RPN2 promotes metastasis of hepatocellular carcinoma cell and inhibits autophagy via STAT3 and NF-κB pathways

Linsheng Huang1,2, Zhiyuan Jian3, Yi Gao1,2, Ping Zhou2, Gan Zhang2, Bin Jiang2, Yi Lv1,4
  • 1National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine, Xi’an, Shaanxi Province, China
  • 2Department of Hepatopancreatobiliary Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province, China
  • 3The First General Surgery Department of the Hospital Affiliated Guilin Medical University, Guilin, Guangxi Province, China
  • 4Department of Hepatobiliary Surgery, The First Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi Province, China
* Equal contribution
Received: April 23, 2019Accepted: August 5, 2019Published: September 3, 2019
https://doi.org/10.18632/aging.102167

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

Abstract

This study aimed to investigate the function and the molecular mechanism of Ribophorin II (RPN2) in regulating Hepatocellular carcinoma (HCC) cell growth, metastasis, and autophagy. Quantitative real-time PCR (qPCR), western blotting analysis, and immunofluorescence assay were utilized to detect the RPN2 expression in HCC cell lines and specimens of HCC patients. We discovered that RPN2 expression was upregulated in HCC cell lines and tissues of HCC patients, which correlated with the low histological grade and low survival rate. Enhanced RPN2 expression stimulated cell proliferation, metastasis, invasion, and epithelial-mesenchymal transition (EMT), and decreased Microtubule-associated protein light chain 3B (LC3B) synthesis and reduced the expression of p62 protein. Further studies suggested that matrix metalloproteinase 9 (MMP-9) was partially upregulated by RPN2 via Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65. Interestingly, we found that phosphorylated RPN2 activated the signal transducer and activator of transcription 3 (STAT3) in HCC cells. It was also accountable for RPN2-stimulated elevated expression of MMP-9 and for invading HCC cells. It can be concluded that over-expression of RPN2 in HCC aggravated the malignant progression into cancerous cells. This research provided new evidences that RPN2 could facilitate tumor invasion by increasing the expression of MMP-9 in HCC cells.