Researches On The Functional Analysis Of PinX1 Gene In Telomerase/Telomere Regulation

The main biological function of telomere is protecting the end of chromosome from end-to-end fusion, recombination and degradation. The telomerase RNP is minimally composed of two essential elements called the protein telomerase reverse transcriptase (TERT) and the single stranded RNA(TR)。PinX1 is an evolutionally conserved nucleolar protein that has been recently demonstrated as a telomerase/ telomere interacting factor in both the humans and the yeasts.Purposes: to further characterize the roles of PinX1 in telomerase/telomere regμlations in human cancers and the influences of PinX1 on telomerase-positive cancer cells. Methods: according to PinX1 mRNA sequence, PinX1 shRNA was designed, and infected into HT1080, HepG2 and U2OS cancer cell lines for stable expressing; Then the influence of silencing PinX1 on cell proliferation and senescence, DNA-damage induced apoptosis, telomerase activity and telomere length were detected in these stable cells; Finally, Myc-POT1 immunoprecipitation(IP) assay were carried out. Resμlts: PinX1 was expressed ubiquitously in various human cell lines. Silencing PinX1 in telomerase-positive cancer cells coμld resμlt in cell senescence, improve sensitivity of DNA-damage induced apoptosis, arose telomere shortening and it`s dysfunction, reduce the association between telomerase and POT1-containing telomeric components. Conclusion: in this study, a novel positive role of PinX1 in telomerase/telomere regμlations was revealed, and the constitutive expression of PinX1 attributes to the telomerase-mediated telomere maintenance and proliferation in cancer cells...