NOP14, which is functionally conserved among eukaryotes, has been implicated in cancer development. Here, we show that NOP14 is poorly expressed in breast cancer cells and invasive breast cancer tissues. In vivo and in vitro studies indicated that NOP14 suppressed the tumorigenesis and metastasis of breast cancer cells. Further investigations revealed that NOP14 enhanced ERα expression and inhibited the Wnt/β-catenin pathway by up-regulating NRIP1 expression. Survival analysis indicated that low NOP14 expression was significantly associated with poor overall survival (P = 0.0006) and disease-free survival (P = 0.0007), suggesting that NOP14 is a potential prognostic factor in breast cancer. Taken together, our findings reveal that NOP14 may suppress breast cancer progression and provide new insights into the development of targeted therapeutic agents for breast cancer.
Our previous studies have shown that platelet endothelial cell adhesion molecule-1 (PECAM-1), a member of the immunoglobulin superfamily, is a critical mediator of anchorage-independent growth and anoikis resistance in lung carcinoma cells. The purpose of this study was to analyze the protein expression of PECAM-1 in non-small-cell lung carcinoma (NSCLC) tissues and its clinical significance in NSCLC patients. By immunohistochemical analysis, high microvessel density (MVD) of PECAM-1 was detected in the stromal tissues of NSCLC. The MVD of PECAM-1 was strongly correlated with the N stage (p = 0.029), M stage (p = 0.001) and clinical stage (p = 0.001) of NSCLC patients. Survival analysis revealed high MVD of PECAM-1 in both primary NSCLC lesions and metastatic lymph node tissues, and these results were found to be significantly correlated with poor overall survival in NSCLC patients (p < 0.001 and p = 0.021, respectively). Moreover, patients with high PECAM-1 MVD had worse overall survival in either adenocarcinoma or EGFR mutation subgroups. Multivariate analysis revealed that the MVD of PECAM-1 was an independent prognostic factor for NSCLC patients. The MVD of PECAM-1 is also a potential predictor for NSCLC patients treated with first-line platinum-based doublet chemotherapy, as high PECAM-1 MVD correlated with worse overall survival. Our results demonstrated that MVD of PECAM-1 could be a potential prognostic factor and therapeutic target in NSCLC.
The overexpression of centromere protein H (CENPH), one of the fundamental components of the human active kinetochore, has been shown to be closely associated with human cancers. However, the mechanism of its transcriptional regulation has not been reported. The aim of the present study was to investigate the regulatory elements for the transcriptional regulation of CENPH in nasopharyngeal carcinoma cells. To characterize the CENPH promoter and identify regulatory elements, we cloned 1015 bp ()975 ⁄ +40 bp) of the 5¢-flanking region of the CENPH gene from immortalized normal nasopharyngeal epithelial cells (Bmi-1 ⁄ NPEC). Functional analysis established a minimal region ()140 ⁄ )87 bp) involved in the regulation of human CENPH promoter activity. Through site-directed mutagenesis, a transactivation assay, chromatin immunoprecipitation, and electrophoretic mobility shift assay, we found that the Sp1 ⁄ Sp3 transcription factors could bind to the CENPH promoter in vitro and in vivo, and that they regulated CENPH promoter activation in human nasopharyngeal carcinoma cells. Furthermore, Sp1 and Sp3 were highly expressed in nasopharyngeal carcinoma cells. Knockdown of Sp1 and Sp3 by small interfering RNA or inhibition of Sp1 and Sp3 activity by mithramycin A decreased CENPH mRNA expression, whereas the exogenous expression of Sp1 and Sp3 upregulated CENPH mRNA expression. Taken together, our results indicate that Sp1 and Sp3 bind to the CENPH minimal promoter and function as a regulator of the transcription of CENPH in human nasopharyngeal carcinomas.
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