Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma

Shusen Zhang; Weidong Shi; Yuyan Chen; Zhiwei Xu; Jia Zhu; Tingting Zhang; Wei Huang; Runzhou Ni; Cuihua Lu; Xiubing Zhang

doi:10.1007/s11010-015-2533-9

Overexpression of SYF2 correlates with enhanced cell growth and poor prognosis in human hepatocellular carcinoma

Mol Cell Biochem. 2015 Dec;410(1-2):1-9. doi: 10.1007/s11010-015-2533-9. Epub 2015 Aug 11.

Authors

Shusen Zhang¹, Weidong Shi², Yuyan Chen³, Zhiwei Xu⁴, Jia Zhu⁴, Tingting Zhang¹, Wei Huang¹, Runzhou Ni¹, Cuihua Lu⁵, Xiubing Zhang⁶

Affiliations

¹ Department of Digestion, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
² Department of Oncology, The Second People's Hospital of Nantong, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
³ Class 5 Grade 13, Clinical Medicine, Medical College, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
⁴ Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China.
⁵ Department of Digestion, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. ntluch@163.com.
⁶ Department of Oncology, The Second People's Hospital of Nantong, Nantong University, Nantong, 226001, Jiangsu, People's Republic of China. xiubingzhang@163.com.

PMID: 26260052
DOI: 10.1007/s11010-015-2533-9

Abstract

SYF2, also known as p29/NTC31/CBPIN, encodes a nuclear protein that interacts with Cyclin D-type binding-protein 1. SYF2 has been reported to be involved in pre-mRNA splicing and cell cycle regulation. In the present study, we observed that SYF2 was obviously upregulated in HCC tumor tissues and cell lines, and its level was positively correlated with the tumor grade and Ki-67 expression, as well as poor prognosis of HCC. In vitro, using serum starvation-refeeding experiment, our results suggested that SYF2 was upregulated in proliferating HCC cells, and was positive correlated with the expression of PCNA and Cyclin D1. In addition, depletion of SYF2 decreased PCNA and Cyclin D1 levels. Accordingly, interference of SYF2 resulted in cells cycle arrest at G1/S phase in Huh7 HCC cells. Furthermore, we found that SYF2 might interact with Cyclin D1 and could confer doxorubicin resistance in HCC cells. These findings revealed that SYF2 might play a regulatory role in the proliferation of HCC cells. In summary, SYF2 may be a novel prognostic marker and serve as a potential therapeutic target in HCC.

Keywords: Cell proliferation; Cyclin D1; Hepatocellular carcinoma; Prognosis; SYF2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Antibiotics, Antineoplastic / pharmacology
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism*
Carcinoma, Hepatocellular / drug therapy
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology
Cell Proliferation* / drug effects
Cyclin D1 / metabolism
Doxorubicin / pharmacology
Drug Resistance, Neoplasm
Female
G1 Phase Cell Cycle Checkpoints
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Liver Neoplasms / drug therapy
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Liver Neoplasms / mortality
Liver Neoplasms / pathology
Male
Middle Aged
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Proliferating Cell Nuclear Antigen / metabolism
RNA Interference
RNA-Binding Proteins
Signal Transduction
Survival Analysis
Time Factors
Transfection
Up-Regulation
Young Adult

Substances

Antibiotics, Antineoplastic
Biomarkers, Tumor
CCND1 protein, human
GCIP-interacting protein p29, human
Nuclear Proteins
Proliferating Cell Nuclear Antigen
RNA-Binding Proteins
Cyclin D1
Doxorubicin