Heterochromatin protein 1γ (HP1γ), which binds to di- or trimethylated lysine 9 on histone H3 (H3K9), plays an important role in chromatin packaging and gene transcriptional regulation. Recently, HP1γ has been implicated in cancer development. However, its clinical relevance and functional role in non-small cell lung cancer (NSCLC) remain elusive. In this study, we found that HP1γ expression was elevated in NSCLC samples at the messenger RNA (mRNA) level compared to adjacent normal lung tissues. In a cohort of 108 NSCLC patients, HP1γ overexpression is significantly associated with N stage (P = 0.003), pathological tumor–node–metastasis (TNM) stage (P = 0.013), smoking status (P = 0.009), and gender (P = 0.042). Patients with a high level of HP1γ expression showed a poorer overall survival rate than those with low HP1γ expression (P = 0.017). Multivariate analysis revealed that HP1γ expression is an independent prognostic marker. We also found knockdown of HP1γ in A549 and NCI-H1975 cells induced apoptosis accompanied with suppressed cell proliferation and colony formation. Consistently, pro-apoptotic proteins, Bax and GADD45α, were upregulated in response to HP1γ depletion. Altogether, our data suggested that HP1γ plays an important role in promoting NSCLC and may represent a novel prognostic biomarker and therapeutic target for the disease.
HP1γ NSCLC Prognosis Proliferation Apoptosis
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This study was supported by the Ministry of Science and Technology of the People’s Republic of China (2011CB944104, 2010CB945101), the National Natural Science Foundation (81172009, 81372168), and the Doctoral Fund of the Ministry of Education of China (20110091120028). The study was also supported by a grant from the “Twelve-Five Plan,” the Major Program of Nanjing Medical Science and Technique Development Foundation (Molecular Mechanism Study on Metastasis and Clinical Efficacy Prediction of Non-small Cell Lung Cancer) and Third Level Training Program of Young Talent Project of Nanjing Health, Nanjing Medical Science and Technology Development Project (QRX11226), and Young Professionals Foundation of Nanjing Chest Hospital. We also thank Dr. Xin Lou for editing our manuscript.
Conflicts of interest
The authors declare that they have no competing interests.
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