Li et al [27] further found that PinX1 is recruited to the area

Li et al. [27] further found that PinX1 is recruited to the area surrounding chromosome by nucleolin during mitosis to promote chromosomes congression. Chen et al. [28]

found that PinX1 binds to Pin2/TRF1 and hTERT at different sites: LPTS/PinX1 (254- 289) binds to Pin2/TRF1, while LPTS/PinX1 (290-328) binds to hTERT. Binding of LPTS/PinX1 (290-328) to hTERT in vitro significantly inhibits telomerase activity, leading to telomere shortening and cell apoptosis. In this buy CRT0066101 study, we successfully constructed PinX1 expression vector pEGFP-C3-PinX1 and found its transfection into NPC cells significantly increased PinX1 mRNA level using RT-PCR, which laid the foundation for study on the roles of PinX1 in NPC cells. Our results also found that overexpression of PinX1 by transfection of pEGFP-C3-PinX1 into NPC cells significantly reduced hTERT mRNA level, telomerase H 89 in vitro activity, NPC cell growth,

migration and wound healing ability, arressted NPC cells in G0/G1 phase and induced cell apoptosis, whereas those phenomena were not found in cells transfected with control vector pEGFP-C3 or treated with lipofectamine alone compared with nontreated NPC cells. These suggest that PinX1 is a potential inhibitor of telomerase activity, in consistence with many other previous reports on tumors. To better understand the role of PinX1 on tumor cells, we also successfully established PinX1-specific siRNA PinX1-FAM-siRNA, transfection of which significantly silenced 70% of endogenous PinX1 mRNA in NPC cells (p < 0.001). However, PinX1 silencing did not alter telomerase activity, and NPC cell growth and migration. This discrepancy to previous studies [22, 24] may be interpreted by the followings:

1) endogenous PinX1 level Succinyl-CoA is already very low in tumor cells, therefore further downregulation has little effect on telomerase activity; 2) silencing PinX1 by transfection of PinX1-FAM-siRNA may be not long enough to observe substantial biological alterations of tumor cells. But no matter how, PinX1-FAM-siRNA can inhibit PinX1 expression in vitro. Although few studies have been conducted on PinX1 silencing, studies by Zhang et al. [22] and Wang et al. [24] confirmed PinX1 is closely related with telomerase activity. Conclusions In conclusion, this study systematically analyzed the roles of PinX1 in NPC 5-8 F cells by oeverexpression or downregulation of PinX1 and found that PinX1 affects NPC cell growth, migration, wound healing ability and cell cycles by inhibiting telomerase activity, suggesting that PinX1 is a potential telomerase inhibitor and has potential therapeutic application in treatment of tumors including NPC.

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