TRIM24 Overexpression Is Common in Locally Advanced Head and Neck Squamous Cell Carcinoma and Correlates with Aggressive Malignant Phenotypes

Zhibin Cui,Jiang Li,Wei Cao,Xiaomeng Song,Wantao Chen,Li Mao,Gnanasekar Munirathinam

doi:10.1371/journal.pone.0063887

Abstract

Tripartite motif-containing 24 (TRIM24), a member of the transcriptional intermediary factor 1 family, functions as a co-regulator that positively or negatively modulates the transcriptional activities of several nuclear receptors. The aim of this study was to investigate TRIM24 expression and its clinical significance in head and neck squamous cell carcinoma. The expression levels of TRIM24 variants were examined in head and neck squamous cell carcinoma (HNSCC) samples and cell lines by real-time PCR and WB. The expression levels of TRIM24 measured in 91 locally advanced HNSCC tumors were measured by immunohistochemistry and correlated with clinical and pathological parameters. The functional role of TRIM24 in HNSCC was further investigated by silencing its expression in HNSCC cell lines. TRIM24 variants were up-regulated in 56 HNSCC samples (P<.001) and 9 HNSCC cell lines (P<.05). TRIM24 protein was overexpressed in 6 of 8 HNSCC cell lines and in 2 of 3 HNSCC samples. Furthermore, 54.95% (50/91) of HNSCC samples exhibited remarkably elevated expression of TRIM24 by immunohistochemistry. Univariate analysis revealed that high TRIM24 expression was associated with worse overall survival (P = .020). In multivariate analysis, TRIM24 expression was identified as an independent predictor of overall survival (P = .030), after adjusting for other clinicopathological parameters. Upon TRIM24 silencing, the proliferation of HNSCC cells was notably inhibited due to the induction of apoptosis. These results suggest that aberrant TRIM24 expression may play an important role in the development of HNSCC and is a promising prognostic indicator for patients with locally advanced HNSCC.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is one of the 10 most common malignancies in the world with more than 500 000 new cases are reported annually
Tripartite Motif-Containing 24 (TRIM24) mRNA levels were higher in HNSCC tissues compared to adjacent normal tissues in the 56 HNSCC patients (Fig. 1D–F)
We found that TRIM24, called TIF-1, was frequently up-regulated at both mRNA and protein levels in HNSCC, in cell lines and primary tumors

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is one of the 10 most common malignancies in the world with more than 500 000 new cases are reported annually. It is widely recognized as a heterogeneous tumor type with various aggressive malignant phenotypes [1]. In vitro studies have suggested that TRIM24 negatively regulates prostate cancer cell proliferation through binding to bromodomain containing 7, which represses androgen receptor transactivation activity [11]. TRIM24 can bind chromatin and the estrogen receptor to activate estrogen-dependent genes associated with cell proliferation and tumor development in breast [12]. The aberrant expression of TRIM24 is significantly associated with poor prognosis patients with breast cancer [13]

Objectives

Methods

Results

Conclusion