Enhanced expression of SETDB1 possesses prognostic value and promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma

Abstract

SETDB1, an H3K9‑specific histone methyltransferase, has been described as a repressed transcription marker which triggers tumorigenesis of many types of human cancer. However, there are few studies elucidating the relationship between SETDB1 and nasopharyngeal carcinoma. In the present study, we confirmed that SETDB1 exhibited higher expression levels in nasopharyngeal carcinoma (NPC) tissues and cell lines, compared to these levels in non‑tumor tissues and a normal human nasopharyngeal epithelial cell line. Kaplan‑Meier analysis showed that higher SETDB1 expression indicated an unfavorable prognosis for NPC patients, making it an independent prognostic factor for NPC in the COX proportional hazards model. In vitro functional studies revealed that upregulation of SETDB1 expression in CNE1 cells promoted cell proliferation, possibly through cell cycle G1/S phase transition. Moreover, it also enhanced cell migration and invasion ability. Downregulation of SETDB1 expression in 5‑8F cells resulted in the opposite response. Overall, the findings indicated that increased expression of SETDB1 may predict poor overall survival and the malignant phenotype of NPC.

Knockdown of SET Domain, Bifurcated 1 suppresses head and neck cancer cell viability and wound-healing ability in vitro

“…The knockdown of SETDB1 increased the apoptosis rate in various cancer types (Richter et al, 2009;Spyropoulou et al, 2014;Wong et al, 2016;Huang et al, 2018). Moreover, Shinoda et al demonstrated the relationship between SETDB1 and caspase-3 (Shinoda et al, 2016).…”

“…lines was higher in each metastatic line compared to its primary cell line. Studies have reported that the expression of SETDB1 significantly increases the risk of melanoma (Ceol et al, 2011), lung cancer (Lindgren et al, 2012), urothelial carcinoma (Wong et al, 2012), glioma (Spyropoulou et al, 2014), ovarian cancer (Hua et al, 2014), prostate cancer (Sun et al, 2014), breast cancer (Liu et al, 2015), hepatocellular carcinoma (Wong et al, 2016), colorectal cancer (Chen et al, 2017), and solid tumors (Huang et al, 2018). With the increased activity of SETDB1, the excess trimethylation of various tumor suppressors may block gene expression, inducing cancer invasion and metastasis.…”

“…In addition, gliomas (Spyropoulou et al, 2014), hepatocellular carcinoma (Wong et al, 2016), nasopharyngeal carcinoma (Huang et al, 2018), solid tumors (Richter et al, 2009), and lung cancer (Rodriguez-Paredes et al, 2014) have been observed to decrease the viability and wound-healing ability of SETDB1 knockdown HNC cells in various cancer types, which is in parallel with studies reporting suppressed SETDB1 expression with siRNA; P16-INK4A is a tumor suppressor protein that plays a role in cell cycle regulation (Wang et al, 2003). It has been reported that P16-INK4A in SETDB1 knockdown cells with increased expression of promoter methylation decreased active cell viability again (Kostaki et al, 2014).…”

“…SETDB1 is essential for embryogenesis , the development (Matsui et al, 2016) and inactivation of the X chromosome, and cellular differentiation (Minkovsky et al, 2014). The overexpression of SETDB1 has been reported to induce the modulation of genes associated with various signaling pathways, including those for tumorigenesis and those that promote cancer invasion and progression (Ceol et al, 2011;Wong et al, 2016;Huang et al, 2018). The increased expression of SETDB1 is correlated with HNC progression in The Cancer Genome Atlas (TCGA) (https://www.cancer.gov).…”

<p>CYLD Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Regulating NDRG1</p>

“…Despite the 5-year overall survival rate of NPC exceeding 80%, the efficacy of NPC treatments plateaued during the previous decade. 22 Genetic factors play an important role in NPC progression and provide a basis for developing novel therapeutic strategies. Here, we investigated the tumor-suppressive role of CYLD in NPC and revealed an underlying CYLD-specific mechanism according to analyses of results from NPC cell lines and clinical specimens.…”