Role of SAR1B on Modulation of Nasopharyngeal Carcinoma Progression via Negative Regulation of Target of Rapamycin Complex 1 Signaling

Abstract

To speculate an autophagy gene, secretion associated Ras related guanosine triphosphatase 1B related signaling pathway for nasopharyngeal carcinoma based on both in vitro and in vivo experiments. 120 nasopharyngeal carcinoma biopsies (pathologically confirmed) were analyzed and the differentially expressed genes were explored. The internal molecular mechanism was further investigated using the human nasopharyngeal carcinoma cell lines, CNE1, HONE1 and C666-1. The cell proliferation capacity examination and the metabolic assays were performed in CNE1 cell line. The subcutaneous xenograft tumor mice model was also established. Secretion associated Ras related guanosine triphosphatase 1B demonstrated a remarkable decreased activity in nasopharyngeal carcinoma tissues compared with sibling paracancerous tissues. The key components in mammalian target of rapamycin complex 1 but not mammalian target of rapamycin complex 2 were greatly enhanced in nasopharyngeal carcinoma tissues. Moreover, the secretion associated Ras related guanosine triphosphatase 1B displayed a significant decreasing expression pattern and the mammalian target of rapamycin complex 1 kept an upward trend as the tumor, node and metastases stage progressed. The clinical significances for nasopharyngeal carcinoma tumor progression were calculated based on statistical analysis. The cell proliferation assay suggested that secretion associated Ras related guanosine triphosphatase 1B manipulated nasopharyngeal carcinoma cell proliferation via mammalian target of rapamycin complex 1/p70 ribosomal protein kinase 1 dependent signaling pathway. At the same time, transfection of secretion associated Ras related guanosine triphosphatase 1B small interfering ribonucleic acid could significantly enhanced the glycolytic capacity and glycolytic reserve of nasopharyngeal carcinoma cells compared with negative control. Silencing of secretion associated Ras related guanosine triphosphatase 1B promoted xenograft tumour growth, which could be greatly suppressed by rapamycin treatment in a dosage-dependent manner. The study shed a variety of insights for nasopharyngeal carcinoma from an innovative direction