Expression and Critical Role of Interleukin Enhancer Binding Factor 2 in Hepatocellular Carcinoma

Shaobing Cheng,Rongliang Tong,Xiaoyu Weng,Kwabena Owusu-Ansah,Wendi Hu,Chuanhui Peng,Lin Zhou,Heng Xiao,Jian Wu,Zhen Lv,Haiyang Xie,Xu Jiang,Chengli Du,Shusen Zheng,Chaofeng Ding

doi:10.3390/ijms17081373

Abstract

Interleukin enhancer binding factor 2 (ILF2), a transcription factor, regulates cell growth by inhibiting the stabilization of mRNA. Currently, its role has gained recognition as a factor in the tumorigenic process. However, until now, little has been known about the detailed role ILF2 plays in hepatocellular carcinoma (HCC). In this study, we investigated the expression levels of ILF2 in HCC tissue with Western blot and immunohistochemical assays. To examine the effect of ILF2 on liver cancer cell growth and apoptosis, small interfering RNAs (siRNAs) targeting ILF2 were recombined to create lentiviral overexpression vectors. Our results showed higher expression levels of ILF2 mRNA and ILF2 protein in HCC tissue compared with matched peritumoral tissue. Expression of ILF2 may regulate cell growth and apoptosis in liver cancer cells via regulation of B-cell lymphoma 2 (Bcl-2), Bcl-2 related ovarian killer (Bok), Bcl-2-associated X protein (BAX), and cellular inhibitor of apoptosis 1 (cIAP1). Moreover, we inoculated nude mice with liver cancer cells to investigate the effect of ILF2 on tumorigenesis in vivo. As expected, a rapid growth was observed in cancer cells inoculated with a lentiviral vector coding Flag-ILF2 (Lenti-ILF2) compared with the control cells. Hence, these results promote a better understanding of ILF2’s potential role as a therapeutic target in HCC.

Highlights

Hepatocellular carcinoma (HCC) is one of the most common solid tumors, with an estimated 782,500 new cases and 745,500 deaths reported in 2012 worldwide [1]
In order to determine the impact of high Interleukin enhancer binding factor 2 (ILF2) expression levels in the prognosis of HCC patients, the Kaplan–Meier method was used to compare the prognosis among HCC patients with high and low ILF2 expression levels in The Cancer Genome Atlas (TCGA) dataset [24]
It has been reported that ILF2 might be highly expressed in HCC specimens, compared to the normal liver, and serves as a potential molecular target of HCC [23], in agreement with their results, we showed that higher ILF2 expression was observed in most HCC cell lines as well as HCC tissues from patients (Figure 1)

Summary

Introduction

Hepatocellular carcinoma (HCC) is one of the most common solid tumors, with an estimated 782,500 new cases and 745,500 deaths reported in 2012 worldwide [1]. Interleukin enhancer binding factor 2 (ILF2), known as nuclear factor 45 (NF45), is encoded by a gene located on human chromosome 1 (1q11-qter and 1p11-p12). It is confirmed by polymerase chain reaction (PCR) amplification of ILF2-specific DNA sequences [4], and is consistent with a prior localization of the NF45 gene to chromosome 1q21.3 by fluorescence in situ hybridization (FISH) [5]. ILF2/NF45 associates with ILF3/NF90 in the nucleus and regulates IL-2 gene transcription at the antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NFAT) DNA target sequence [6]. The regulation and function of ILF2 have been extensively investigated, the biological functions as well as the molecular mechanisms of ILF2 in tumorigenesis and tumor progression have not been fully demonstrated

Methods

Results

Conclusion