Abstract
BackgroundHuman interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, however, its function in inhibiting telomerase activity of tumor cells is not well documented. Here we show that PinX1 is essential for down-regulation telomerase activity of nasopharyngeal carcinoma.MethodsExpression 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.ResultsTransfection 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.ConclusionsPinX1 may play important roles in NPC proliferation, migration and apoptosis and has application potential in tumor-targeted gene therapy.
Highlights
Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene
We first confirmed the successful construction of PinX1 expression vector pEGFP-C3-PinX1 by digestion with
PinX1 mRNA level in cells transfected with PinX1-FAM-siRNA reduced by 70% compared with that in untreated cells (p < 0.05)
Summary
Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, its function in inhibiting telomerase activity of tumor cells is not well documented. We show that PinX1 is essential for down-regulation telomerase activity of nasopharyngeal carcinoma. Nasopharyngeal carcinoma (NPC) is one of the most incident and dangerous malignant tumors in southern provinces of China. 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%. Systemic and local side effects caused by chemotherapy greatly humbled the patient physically and psychologically. It 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
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