Dysregulation of zinc finger protein, X-linked (ZFX) impairs cell proliferation and induces apoptosis in human oral squamous cell carcinorma.

Hongzhi Ma,Ru Wang,Ling Feng,Jugao Fang,Meng Lian,Qian Shi,Fan Yang,Haizhou Wang

doi:10.1007/s13277-015-3292-7

Abstract

Zinc finger protein, X-linked (ZFX) is a transcriptional factor involved in many physiological processes such as embryonic stem cell survival and self-renewal. Though ZFX dysfunctions have been identified in variant human diseases and especially in cancers, its pathological roles have not been fully addressed. Here, we explored the relationship between ZFX expression and squamous cell carcinoma (SCC) of the tongue. We found that ZFX expression was significantly higher in tongue SCC tumors as compared to tumor-adjacent normal tissues. Furthermore, ZFX knockdown impeded cell proliferation, impaired colony formation ability, and lead to cell cycle arrest while induced cell apoptosis in human tongue squamous cell carcinoma cell line Tca-8113. Our results provide evidence suggesting that ZFX overexpression is associated with the development of tongue SCC and ZFX knockdown is a potential treatment for tumor suppression.

Highlights

Tongue squamous cell carcinoma (SCC) is the most common malignant type in head and neck squamous cell carcinoma (HNSCC), which is among the top ten leading cancers worldwide [1]
X-linked (ZFX) which is encoded by X-linked ZFX gene is a Cys2His2 zinc finger (C2H2-ZF) transcriptional factor composed of three functional domains including a DNA-binding domain containing 13 C2H2-type zinc fingers, an acidic transcriptional activation domain, and a nuclear localization sequence
The relationship between ZFX and tongue SCC remains poorly understood. As both tongue SCC and laryngeal squamous cell carcinoma belong to HNSCC, here we examined the expression status of ZFX and unraveled significant expression differences between tumors and adjacent normal tissues derived from tongue SCC patients

Summary

Introduction

Tongue squamous cell carcinoma (SCC) is the most common malignant type in head and neck squamous cell carcinoma (HNSCC), which is among the top ten leading cancers worldwide [1]. Though remarkable progress has been achieved in clinical and basic research in the past three decades, the 5-year survival rate of tongue SCC patients showed little improvement and remained about 50 % [2]. Another major problem is that most tongue SCC cases showed lymph node metastasis at diagnosis, which indicated poor prognosis, and effective treatment are still underway at present. Cys2His zinc finger (C2H2-ZF) proteins are the major class of DNA-binding proteins and have been implicated in diverse biological processes such as cell proliferation differentiation and cell survival while their dysfunctions have been linked to multiple human diseases including variant types of cancer [4]. In consistent with the role of C2H2-ZF proteins in cancer development, previous studies from our lab have shown that ZFX is aberrantly upregulated in human laryngeal squamous cell carcinoma and ZFX knockdown impaired cancer cell proliferation and apoptosis [7]

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Results

Conclusion