Overexpression of HP1γ is associated with poor prognosis in non-small cell lung cancer cell through promoting cell survival

Heterochromatin protein 1 gamma (HP1 gamma), which binds to di- or trimethylated lysine 9 on histone H3 (H3K9), plays an important role in chromatin packaging and gene transcriptional regulation. Recently, HP1 gamma 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 HP1 gamma 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, HP1 gamma 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 HP1 gamma expression showed a poorer overall survival rate than those with low HP1 gamma expression (P=0.017). Multivariate analysis revealed that HP1 gamma expression is an independent prognostic marker. We also found knockdown of HP1 gamma in A549 and NCI-H1975 cells induced apoptosis accompanied with suppressed cell proliferation and colony formation. Consistently, pro-apoptotic proteins, Bax and GADD45a, were upregulated in response to HP1 gamma depletion. Altogether, our data suggested that HP1 gamma plays an important role in promoting NSCLC and may represent a novel prognostic biomarker and therapeutic target for the disease.