Radiotherapy is the primary and most important treatment for nasopharyngeal carcinoma (NPC). Cancer stem-like cells (CSCs) have been shown to be resistant to radiation. The phosphatase and tensin homolog deleted on chromosome 10 (PTEN) tumor suppressor gene has been suggested to play a role in stem cell self-renewal. In the present study, we sorted PTEN−/+ cells using a flow cytometer. The clone formation assay showed that PTEN− cells were more radioresistant than PTEN+ NPC cells. We found that PTEN− cells demonstrated a significant increase in tumorsphere formation and CSCs markers compared with PTEN+ cells. Silencing the expression of PTEN with siRNA resulted in increased expression of p-AKT, active β-catenin and Nanog. siPTEN cells irradiated showed more radioresistant and DNA damage than parental cells. We also confirmed that down-regulation of β-catenin expression with shRNA resulted in a reduced percentage of side population cells and expression of Nanog. shβ-catenin cells significantly decreased survivin expression at 4 Gy irradiation in PTEN− cells compared with PTEN+ cells. In siPTEN cells, β-catenin staining shifted from the cytoplasmic membrane to the nucleus. Furthermore, immunofluorescence showed that following irradiation of PTEN− cells, at 4 Gy, active β-catenin was mainly found in the nucleus. Immunohistochemistry analysis also demonstrated that the PTEN−/p-AKT+/β-catenin+/Nanog+ axis may indicate poor prognosis and radioresistance in clinical NPC specimens. Thus, our findings strongly suggest that PTEN− cells have CSCs properties that are resistant to radiation in NPC. PTEN exerts these effects through the downstream effector PI3K/AKT/β-catenin/Nanog axis which depends on nuclear β-catenin accumulation.
Maintenance of genomic diversity is critically dependent on gene regulation at the transcriptional level. This occurs via the interaction of regulatory DNA sequence motifs with DNA-binding transcription factors. The zinc finger, BED-type (ZBED) gene family contains major DNA-binding motifs present in human transcriptional factors. It encodes proteins that present markedly diverse regulatory functions. ZBED1 has similar structural and functional properties to its
Drosophila
homolog DNA replication-related element-binding factor (DREF) and plays a critical role in the regulation of transcription. ZBED1 regulates the expression of several genes associated with cell proliferation, including cell cycle regulation, chromatin remodeling and protein metabolism, and some genes associated with apoptosis and differentiation. In the present review, the origin, structure and functional role of ZBED1 were comprehensively assessed. In addition, the similarities and differences between ZBED1 and its
Drosophila
homolog DREF were highlighted, and future research directions, particularly in the area of clinical cancer, were discussed.
The Naples prognostic score (NPS) is an effective inflammatory and nutritional scoring system widely applied as a prognostic factor in various cancers. We aimed to analyze the prognostic value of the NPS in patients diagnosed with non-small-cell lung cancer (NSCLC). We prospectively collected 395 patients diagnosed with NSCLC between January 2016 and December 2018 in two university-affiliated hospitals. Patients were divided into three groups according to their pretreatment NPS (Group 0: NPS = 0; Group 1: NPS = 1–2; Group 2: NPS = 3–4). Kaplan–Meier survival curves indicated that patients with higher NPS had a poorer overall survival (OS) and progress-free survival (PFS) (both P < 0.05). NPS was further confirmed as an independent prognostic factors of OS and PFS by multivariable survival analysis (both P < 0.05). Furthermore, stratifying by TNM stage, NPS also has significant predictive performance for OS and PFS in both early (I–IIIA) and advanced (IIIB–IV) stage NSCLC (all P < 0.05). The time-dependent receiver operating characteristic curve analysis demonstrated that NPS was more superior to other prognostic factors in predicting OS and PFS. In conclusion, NPS may serve as an effective indicator to predict OS and PFS in NSCLC patients regardless of TNM stage.
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