The expression and significance of the enhancer of zeste homolog 2 in lung adenocarcinoma

Abstract

Abstract. Lung adenocarcinoma, with increased incidence in the world, exhibits poor prognosis and is usually resistant to conventional chemotherapy due to drug resistance. The enhancer of zeste homologue 2 (EZH2), a histone methyltransferase, plays a key role in tumorigenesis and cancer development through chromatin remodeling in various types of cancer. However, its potential role in lung adenocarcinoma has not been well defined. In this study, the expression of EZH2 was examined in lung adenocarcinoma tissues and cell lines. Most interestingly, EZH2 overexpression was detected in tumor tissue and significantly correlated with histological differentiation, pathological tumor-node-metastasis stage and smoking history, but not with gender or age. Furthermore, EZH2 overexpression was also detected in cisplatin-resistant cancer cells rather than cisplatin-sensitive cells. Short hairpin RNA targeted against EZH2 inhibited cell proliferation and migration, and led to G(2)/M cell cycle arrest and apoptosis in both cisplatin-resistant and cisplatin-sensitive cell lines. Moreover, EZH2 knockdown enhanced cisplatin sensitivity of cisplatin-resistant cells and reduced the expression levels of multidrug resistance-related protein 1. Our study suggests that EZH2 contributes to the progression of lung adenocarcinoma, and the deletion of EZH2 inhibits cancer and resensitizes cells to cisplatin in lung adenocarcinoma.

Involvement of enhancer of zeste homolog 2 in cisplatin-resistance in ovarian cancer cells by interacting with several genes

“…Rizzo et al observed the EZH2 is overexpressed in ovarian cancer stem cell-like side populations and is associated with drug resistance (29). A similar role for EZH2 has been reported in lung cancer (30). The present study further investigated EZH2 and found that it was downregulated in cisplatin-sensitive ovarian cancer cells.…”

Epigenetics of lung cancer

“…Higher expression of the PRC2 protein, EZH2, in NSCLC tumor tissue has been associated with worse overall [112, 118, 219] and disease-free survival [112] in several studies[117]. Likewise, BMI-1 expression has also been correlated with poorer patient outcomes [107, 121, 220], and amplification and concordant overexpression of the PcG, PHC3 , has recently been associated with poorer outcomes in NSCLC [221].…”

“…A number of studies have reported an association between altered expression of a variety of miRNA and sensitivity to gefitinib [236–241], erlotinib [242, 243], cisplatin [244–259], and radiotherapy [253, 260–265]. Elevated expression of HOTAIR [223] and EZH2 [117] have also each been associated with cisplatin-resistance.…”

EZH2: Not EZHY (Easy) to Deal

“…Like other cancer types, accumulation of several genetic and epigenetic aberrations has been implicated in the initiation and progression of lung cancer. Focusing on the role of histone methyltransferase EZH2 in the pathogenesis of lung cancer, recent evidences suggests that EZH2 over-expression and polycomb mediated H3K27me3 promote malignancy in various lung cancer types including SCLC and NSCLCs, which is commonly associated with poor prognosis (78–80). In a recent study, Coe et al found a strong correlation between deregulation of E2F-Rb pathway in 96% SCLC samples and EZH2 over-expression (81).…”