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PinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells

DOI: 10.1186/1756-9966-31-12

Keywords: PinX1, Telomerase inhibitor, Proliferation, Migration, Apoptosis, Cell cycle, Human nasopharyngeal carcinoma

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Abstract:

Expression vectors of human PinX1 (pEGFP-C3-PinX1) and its small interfering RNA (PinX1-FAM-siRNA) were constructed and transfected into NPC. Their effects on mRNA of telomerase catalytic subunit (hTERT), telomerase activity, cell proliferation, cell migration, wound healing, cell cycles and apoptosis were examined using semi-quantitative RT-PCR, stretch PCR, MTT assay, Transwell, scratch assay and flow cytometry, respectively.Transfection of pEGFP-C3-PinX1 and PinX1-FAM-siRNA increased and reduced PinX1 mRNA by 1.6-fold and 70%, respectively. Over-expression of PinX1 decreased hTERT mRNA by 21%, reduced telomerase activity, inhibited cell growth, migration and wound healing ability, arrested cells in G0/G1 phase, and increased apoptotic index. In contrast, down-regulation of PinX1 did not alter the above characteristics.PinX1 may play important roles in NPC proliferation, migration and apoptosis and has application potential in tumor-targeted gene therapy.Nasopharyngeal carcinoma (NPC) is one of the most incident and dangerous malignant tumors in southern provinces of China. Genetic factors and environmental factors including Epstein-Barr virus are the two major risk factors for NPC. Radiotherapy along with other auxiliary methods such as chemotherapy is used to treat NPC. Although equipments and technologies in radiotherapy and chemotherapy have been greatly advanced in recent years, the 5-year survival rate of patients with NPC remains about 70%. In addition, systemic and local side effects caused by chemotherapy greatly humbled the patient physically and psychologically. Therefore, it is of importance to study the etiology of NPC and explore new, safe and effective modalities for NPC therapy.Telomerase is well known for its role in the development of malignant tumors. Studies from our group and others [1,2] have found enhanced mRNA level of telomerase catalytic subunit (TERT) and telomerase expression in 88% of NPC specimens and NPC cell line HNE1.Antisense nucl

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