title: PinX1 suppresses tumorigenesis by negatively regulating telomerase/telomeres in colorectal carcinoma cells and is a promising molecular marker for patient prognosis.
abstract: 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-fluorouracil-based adjuvant chemotherapy were enrolled in this study. The expression dynamics of PinX1 was detected by immunohistochemistry in the CRC patients and 25 normal colonic mucosa controls. PinX1 expression was significantly reduced in tumor tissues as compared to normal tissues, and the rate of PinX1 protein low/negative expression in CRC and normal tissues was 60% (52/86) and 24% (6/25), respectively (P=0.037). In addition, PinX1 downregulation was significantly associated with short overall survival (P=0.016) and disease-free survival (P=0.042) in CRC patients. Cox proportional hazards model further revealed that PinX1 expression was an independent factor in predicting overall survival and disease-free survival for CRC patients. Furthermore, we demonstrated that ectopic overexpression of PinX1 in CRC cells inhibited their proliferation, promoted apoptosis, repressed telomerase activity, and induced telomere shortening. These findings suggest that PinX1 may be a prognostic biomarker for CRC patients' survival and that it inhibits cell proliferation and promotes apoptosis by repressing telomerase activity and inducing telomere shortening. Targeting PinX1 may therefore provide a novel therapeutic strategy for CRC patients.
authors.affiliation: Department of Radiotherapy.
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
authors.affiliation: Department of Radiotherapy.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Radiotherapy.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Ding
authors.affiliation: Department of Radiotherapy.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiotherapy.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Lung Cancer.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Colorectal Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin.
authors.forename: Jiefu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy.
authors.forename: Puchun
authors.initials: P
authors.lastname: Er
authors.affiliation: Department of Radiotherapy.
authors.forename: Minghan
authors.initials: M
authors.lastname: Qiu
authors.affiliation: Department of Radiotherapy.
authors.forename: Xianliang
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Radiotherapy.
authors.forename: Yihang
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Radiotherapy.
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy.
authors.forename: Lujun
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-Sen University, Guangzhou, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.affiliation: Department of Radiotherapy.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Radiotherapy.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Radiotherapy.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Pang
keywords: PinX1; apoptosis; cell proliferation; colorectal carcinoma; prognostic biomarker; telomerase; telomere