PinX1 without the G-patch motif suppresses proliferation, induces senescence, but does not inhibit telomerase activity in colorectal cancer SW480 cells.
نویسندگان
چکیده
Evidence suggests that Pin2/TRF1-interacting protein X1 (PinX1) inhibits telomerase activity in many types of cancer cells. G-patch is a motif in the PinX1 protein; however, the function of G-patch in colorectal cancer cells has not been definitively elucidated. The present study investigated the antitumor activities of different PinX1 fragments in vitro, and explored the molecular mechanisms responsible for these effects. SW480 cells were transfected with pEGFP-A1-PinX1 1-328 (intact) or pEGFP-A1-PinX1 69-328 (truncated). Flow cytometry was used to observe apoptosis and the cell cycle of SW480 cells transfected with intact PinX1 or truncated PinX1. The apoptosis-related proteins, caspase 3, 8 and 9, were detected by western blotting. Our results indicate that both intact and truncated PinX1 induced apoptosis, G1 arrest, and cellular senescence. However, truncated PinX1 showed no effects on telomerase activity. Why PinX1 without G-patch has similar antitumor activities as intact PinX1 remains unclear. The mechanisms of G-patch require elucidation in subsequent studies. Finally, we detected the protein and mRNA levels of PinX1 and caspase 3, 8 and 9 in colorectal cancer specimens and confirmed that levels of PinX1 and caspase 3, 8 and 9 expression were closely linked to the poor prognosis of colorectal cancer.
منابع مشابه
The telomerase inhibitor Gno1p/PINX1 activates the helicase Prp43p during ribosome biogenesis
We provide evidence that a central player in ribosome synthesis, the ribonucleic acid helicase Prp43p, can be activated by yeast Gno1p and its human ortholog, the telomerase inhibitor PINX1. Gno1p and PINX1 expressed in yeast interact with Prp43p and the integrity of their G-patch domain is required for this interaction. Moreover, PINX1 interacts with human PRP43 (DHX15) in HeLa cells. PINX1 di...
متن کاملSilencing PinX1 compromises telomere length maintenance as well as tumorigenicity in telomerase-positive human cancer cells.
The nucleolar protein PinX1 has been proposed to be a putative tumor suppressor due to its binding to and inhibition of the catalytic activity of telomerase, an enzyme that is highly expressed in most human cancers in which it counteracts telomere shortening-induced senescence to confer cancer cell immortalization. However, the role of PinX1 in telomere regulation, as well as in cancer, is stil...
متن کاملPinX1 suppresses tumorigenesis by negatively regulating telomerase/telomeres in colorectal carcinoma cells and is a promising molecular marker for patient prognosis
PinX1 plays positive and negative roles in the maintenance of telomerase and telomeres, as well as in tumorigenesis. The aim of the present study was to investigate the expression and clinical significance of PinX1 in colorectal carcinoma (CRC) and to determine the effect of PinX1 on CRC cell proliferation and apoptosis. A total of 86 CRC patients treated with radical resection and 5-fluorourac...
متن کاملPinX1 regulation of telomerase activity and apoptosis in nasopharyngeal carcinoma cells
BACKGROUND 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, 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 n...
متن کاملPinX1 Is a Potential Prognostic Factor for Non-Small-Cell Lung Cancer and Inhibits Cell Proliferation and Migration
PinX1 has been identified as a suppressor of telomerase enzymatic activity. However, the tumour-suppressive roles of PinX1 in different types of human cancers are unclear. PinX1 expression status and its correlation with clinicopathological features in non-small-cell lung cancer (NSCLC) have not been investigated. Accordingly, in this study, we aimed to evaluate the roles of PinX1 in NSCLC. Pin...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Oncology reports
دوره 32 1 شماره
صفحات -
تاریخ انتشار 2014