Abstract
BackgroundPIN2/TRF1-interacting telomerase inhibitor1 (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Moreover, loss of PinX1 has been detected in many human malignancies. However, the possible involvement of PinX1 and its clinical/prognostic significance in urothelial carcinoma of the bladder (UCB) are unclear.MethodsThe PinX1 expression profile was examined by quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry (IHC) in UCB tissues and adjacent normal urothelial bladder epithelial tissues. PinX1 was overexpressed and silenced in UCB cell lines to determine its role in tumorigenesis, development of UCB, and the possible mechanism.ResultsPinX1 expression in UCB was significantly down-regulated at both mRNA and protein level as compared with that in normal urothelial bladder epithelial tissues. PinX1 levels were inversely correlated with tumor multiplicity, advanced N classification, high proliferation index (Ki-67), and poor survival (P < 0.05). Moreover, overexpression of PinX1 in UCB cells significantly inhibited cell proliferation in vitro and in vivo, whereas silencing PinX1 dramatically enhanced cell proliferation. Overexpression of PinX1 resulted in G1/S phase arrest and cell growth/proliferation inhibition, while silencing PinX1 led to acceleration of G1/S transition, and cell growth/proliferation promotion by inhibiting/enhancing telomerase activity and via the p16/cyclin D1 pathway.ConclusionsThese findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.
Highlights
PIN2/TRF1-interacting telomerase inhibitor1 (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase
PIN2/TRF1-interacting telomerase inhibitor1 (PinX1) is a newly cloned gene mapped to chromosome 8p23.1 that consists of seven exons in humans and is a region frequently associated with loss of heterozygosity in a variety of human malignancies [6,7,8,9,10]
Results quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis of PinX1 expression in bladder tissues Our qRT-PCR results showed that PinX1 mRNA expression was downregulated in eight out of 10 urothelial carcinoma of the bladder (UCB) samples compared with the paired normal bladder tissues (Figure 1A)
Summary
PIN2/TRF1-interacting telomerase inhibitor (PinX1) was recently suggested as a putative tumor suppressor in several types of human cancer, based on its binding to and inhibition of telomerase. Loss of PinX1 has been detected in many human malignancies. The possible involvement of PinX1 and its clinical/prognostic significance in urothelial carcinoma of the bladder (UCB) are unclear. PIN2/TRF1-interacting telomerase inhibitor (PinX1) is a newly cloned gene mapped to chromosome 8p23.1 that consists of seven exons in humans and is a region frequently associated with loss of heterozygosity in a variety of human malignancies [6,7,8,9,10]. Chang et al reported that high significance between a single-nucleotide polymorphism on the PinX1 gene and lower bladder cancer risk [12]. We investigated the clinicopathological and prognostic significance as well as the potential role of PinX1 in the development and progression of UCB
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