Pathway-focused PCR array profiling of CAL-27 cell with over-expressed ZNF750.

Li Pan,Wenqiang Tang,Haiying Chen,Shuangfeng Chen,Cong Xu,Keyi Li,Hongli Yang,Zhen Meng

doi:10.18632/oncotarget.23075

Abstract

Zinc-finger protein 750 (ZNF750) is the potential anti-cancer gene in oral squamous cell carcinoma (OSCC). The present study was to investigate the expression changes of ZNF750 in OSCC tissue and to reveal the induction of altered mRNA expression profiles caused by over-expressed ZNF750 in CAL-27 cell. The expression level of ZNF750 in tissue specimens from OSCC patients was detected by immunohistochemistry. Gene expression profiling was performed using Human Signal Transduction PathwayFinder RT2 Profiler™ PCR Array. The expression changes of 84 key genes representing 10 signal transduction pathways in human following over-expressed ZNF750 in CAL-27 cell was examined. The expression of ZNF750 protein was reduced in OSCC tissues. The R2 PCR Array analysis revealed that 39 of the 84 examined genes that changed at least a two-fold between control and ZNF750 groups. These genes related to oxidative stress, WNT, JAK/STAT, TGFβ, NF-kappaB (NFκB), p53, Notch, Hedgehog, PPAR and Hypoxia signaling. ZNF750 could inhibit the candidate genes ATF4, SQSTM1, HMOX1, CCND1, TNF-alpha, TNFSF10 and FOSL1 but activate CDKN1A and EMP1. Our studies suggest that ZNF750 can regulate signaling pathways that related to proliferation, cell cycle, inflammation and oxidative stress in CAL-27 cell.

Highlights

Oral cancer is an aggressive and lethal disease with no significant improvements in the overall survival in the last decades [1]
Our studies suggest that Zinc-finger protein 750 (ZNF750) can regulate signaling pathways that related to proliferation, cell cycle, inflammation and oxidative stress in CAL-27 cell
The bar diagram indicate the clustering of differential expression genes in 10 signal transduction pathway, these 10 signal pathway were related to cell proliferation, cell apoptosis, cell cycle, inflammation, hypoxia and oxidative stress

Summary

Introduction

Oral cancer is an aggressive and lethal disease with no significant improvements in the overall survival in the last decades [1]. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias [2]. The mortality and morbidity rates of oral squamous cell carcinoma (OSCC) remain high [3]. It is reported that Zinc-finger protein 750 (ZNF750) is normally expressed in keratinocytes [4], and is key factor to turn on the terminal epidermal differentiation gene program. ZNF750 repress epidermal progenitor genes and induce differentiation genes [5]. The abnormal expression of ZNF750 in oral keratinocyte may lead to imbalance of cell proliferation and development to malignant tumor. As for ZNF750 is a newly found lineage-specific tumor suppressor in squamous cell carcinoma [6], there is still a great deal of work to be done to identify the effect of ZNF750 on OSCC

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