PinX1 suppresses tumorigenesis by negatively regulating telomerase/telomeres in colorectal carcinoma cells and is a promising molecular marker for patient prognosis.
PinX1 suppresses tumorigenesis by negatively regulating telomerase/telomeres in colorectal carcinoma cells and is a promising molecular marker for patient prognosis.
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PinX1 通过负向调节结直肠癌细胞中的端粒酶/端粒来抑制肿瘤发生，是一种有前途的患者预后分子标志物
DOI：
10.2147/ott.s103141
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发表时间：
2016
影响因子：
4
通讯作者：
Pang Q
中科院分区：
文献类型：
--
作者：
Qian D;Cheng J;Ding X;Chen X;Chen X;Guan Y;Zhang B;Wang J;Er P;Qiu M;Zeng X;Guo Y;Wang H;Zhao L;Xie D;Yuan Z;Wang P;Pang Q
PinX 1在端粒酶和端粒的维持以及肿瘤发生中起着积极和消极的作用。本研究旨在探讨PinX 1在结直肠癌中的表达及其临床意义，并探讨PinX 1对结直肠癌细胞增殖和凋亡的影响。共86例接受根治性切除和5-氟尿嘧啶为基础的辅助化疗的结直肠癌患者入选本研究。采用免疫组化法检测PinX 1在结直肠癌患者和25例正常结肠黏膜中的表达动态。PinX 1蛋白在大肠癌组织中的表达明显低于正常组织（P=0.037），在大肠癌和正常组织中的低表达率分别为60%（52/86）和24%（6/25）。此外，PinX 1下调与CRC患者的短总生存期（P=0.016）和无病生存期（P=0.042）显著相关。考克斯比例风险模型进一步揭示PinX 1表达是预测CRC患者总生存期和无病生存期的独立因素。此外，我们证明了PinX 1在结直肠癌细胞中的异位过表达抑制其增殖，促进凋亡，抑制端粒酶活性，并诱导端粒缩短。这些发现表明PinX 1可能是CRC患者生存的预后生物标志物，并且它通过抑制端粒酶活性和诱导端粒缩短来抑制细胞增殖并促进细胞凋亡。因此，靶向PinX 1可能为CRC患者提供一种新的治疗策略。
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.