Oncotarget

Research Papers:

Knockdown of Golgi phosphoprotein 2 inhibits hepatocellular carcinoma cell proliferation and motility

Yiming Liu, Xiaodi Zhang, Ting Sun, Junchang Jiang, Ying Li, Mingliang Chen, Zhen Wei, Weiqin Jiang and Linfu Zhou _

PDF  |  HTML  |  How to cite

Oncotarget. 2016; 7:21404-21415. https://doi.org/10.18632/oncotarget.7271

Metrics: PDF 2966 views  |   HTML 2891 views  |   ?  


Abstract

Yiming Liu1, Xiaodi Zhang1, Ting Sun2, Junchang Jiang3, Ying Li4, Mingliang Chen1, Zhen Wei5, Weiqin Jiang6, Linfu Zhou1

1Medical Biotechnology Laboratory, Zhejiang University School of Medicine, Hangzhou 310058, China

2Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China

3Department of Pathology, RunRun-Shaw Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou 310016, China

4Clinical Laboratory, Children’s Hospital Affiliated to Zhejiang University School of Medicine, Hangzhou 310003, China

5Laboratory Animal Center, Zhejiang University School of Medicine, Hangzhou 310058, China

6Cancer Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China

Correspondence to:

Linfu Zhou, e-mail: [email protected]

Weiqin Jiang, e-mail: [email protected]

Keywords: Golgi phosphoprotein 2, hepatocellular carcinoma, siRNA, cell proliferation, biomarker

Received: October 15, 2015     Accepted: January 24, 2016     Published: February 08, 2016

ABSTRACT

Golgi phosphoprotein 2 (GP73) is highly expressed in hepatocellular carcinoma (HCC) cells, where it serves as a biomarker and indicator of disease progression. We used MTS assays, anchorage-independent cell colony formation assays and a xenograft tumor model to show that GP73-specific siRNAs inhibit HCC proliferation in HepG2, SMMC-7721, and Huh7 cell lines and in vivo. Following GP73 silencing, levels of p-Rb, a factor related to metastasis, were reduced, but cell cycle progression was unaffected. Our results suggest that GP73 silencing may not directly suppress proliferation, but may instead inhibit cell motility. Results from proliferation assays suggest GP73 reduces expression of epithelial mesenchymal transition (EMT)-related factors and promotes cell motility, while transwell migration and invasion assays indicated a possible role in metastasis. Immunofluorescence co-localization microscopy and immunoblotting showed that GP73 decreases expression of N-cadherin and E-cadherin, two key factors in EMT, which may in turn decrease intracellular adhesive forces and promote cell motility. This study confirmed that GP73 expression leads to increased expression of EMT-related proteins and that GP73 silencing reduces HCC cell migration in vitro. These findings suggest that GP73 silencing through siRNA delivery may provide a novel low-toxicity therapy for the inhibition of tumor proliferation and metastasis.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 7271