摘要
背景:在各种类型的癌症中经常发现12p12-13的杂合性缺失(LOH)。 LOH12CR1是位于12p12-13区域内的七个关键基因之一。由LOH12CR1编码的蛋白质参与溶酶体的功能,其它功能仍不清楚。 目的:本研究旨在探讨LOH12CR1在结直肠癌发生中的潜在作用。 方法:采用免疫组化染色法检测174例结直肠癌组织中LOH12CR1的蛋白水平。通过回顾性研究进一步研究了LOH12CR1表达与患者预后之间的相关性。通过在四种结肠直肠癌细胞系和一种正常细胞系中敲低或过表达LOH12CR1来检查肿瘤抑制能力。 结果:在结直肠癌组织中观察到LOH12CR1蛋白显着降低(P <0.001)。通过下调p16INK4a和p21WAF1 / CIP1,LOH12CR1的敲低促进了结肠直肠癌细胞增殖,集落形成和加速的G1 / S细胞周期转变,而LOH12CR1的异位表达显示出相反的效果。 LOH12CR1的蛋白水平与p16INK4a和p21WAF1 / CIP1的表达密切相关。最重要的是,LOH12CR1的蛋白水平与结直肠癌的临床预后呈负相关。 结论:目前的结果表明LOH12CR1可能作为肿瘤抑制因子发挥作用。因此,LOH12CR1的功能丧失可能是结直肠癌发展的潜在驱动因素。检测LOH12CR1可用作结直肠癌患者的诊断和治疗评估方法。
关键词: LOH12CR1,肿瘤抑制因子,结肠直肠癌,细胞周期,G1 / S停滞,p16,p21。
Current Molecular Medicine
Title:LOH12CR1 is a Novel Tumor Suppressor Inhibiting Tumor Growth Through Deregulation of G1/S Checkpoint in Human Colorectal Carcinoma
Volume: 18 Issue: 1
关键词: LOH12CR1,肿瘤抑制因子,结肠直肠癌,细胞周期,G1 / S停滞,p16,p21。
摘要: Background: Loss of heterozygosity (LOH) of 12p12-13 has been frequently found in various types of cancer. LOH12CR1 is one of the seven critical genes located within the 12p12-13 region. The protein encoded by LOH12CR1 is involved in the function of lysosomes and its other functions are still unclear.
Objective: The aim of this study is to investigate the potential roles of LOH12CR1 in the development of colorectal cancer.
Methods: A total of 174 colorectal cancer tissues were used to examine the protein level of LOH12CR1 by immunohistochemistry staining. The correlation between LOH12CR1 expression and the patient prognosis was further investigated through retrospective study. The tumor suppression capacity was examined by knockdown or overexpression of LOH12CR1 in four colorectal cancer cell lines and one normal cell line.
Results: Significant decrease of LOH12CR1 protein was observed in colorectal cancerous tissues (P<0.001). Knockdown of LOH12CR1 promoted colorectal cancer cell proliferation, colony formation, and accelerated G1/S cell cycle transition through downregulation of p16INK4a and p21WAF1/CIP1, while ectopic expression of LOH12CR1 displayed the opposite effects. The protein level of LOH12CR1 was well correlated with the expression of p16INK4a and p21WAF1/CIP1. Most importantly, the protein level of LOH12CR1 negatively correlated with clinical prognosis of colorectal carcinomas.
Conclusion: The present results suggest that LOH12CR1 might function as a tumor suppressor. Thus, loss of function of LOH12CR1 might be a potential driver in the development of colorectal carcinoma. Detection of LOH12CR1 could be used as a method for diagnosis and therapeutic assessment of patients with colorectal cancer.
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LOH12CR1 is a Novel Tumor Suppressor Inhibiting Tumor Growth Through Deregulation of G1/S Checkpoint in Human Colorectal Carcinoma, Current Molecular Medicine 2018; 18 (1) . https://dx.doi.org/10.2174/1566524018666180608084005
DOI https://dx.doi.org/10.2174/1566524018666180608084005 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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