Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer
Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer
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新基因gankyrin的过度表达与结直肠癌的恶性表型相关
DOI：
10.4161/cbt.9.2.10283
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发表时间：
2010-01-01
影响因子：
3.6
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Tang, Shanhong;Yang, Guitao;Fan, Daiming
甘丙肽受体相关结合蛋白（Gankyrin）是一种小且高度保守的蛋白质，与p28基因产物相同，被发现与肝癌和食管癌的恶性表型有关。然而，甘丙肽受体相关结合蛋白在结直肠癌（CRC）中的作用仍不清楚。在本研究中，对人CRC细胞系和临床组织样本中甘丙肽受体相关结合蛋白的mRNA和蛋白质表达进行了评估，并与临床病理特征相关联。还研究了甘丙肽受体相关结合蛋白调节CRC细胞恶性表型的可能机制。结果表明，与对照组相比，甘丙肽受体相关结合蛋白在CRC组织和细胞系中明显过表达，并且甘丙肽受体相关结合蛋白的表达与CRC的TNM分期和转移相关。通过将PhkitNeo - hGankyrin质粒转染到Lovo细胞中过表达甘丙肽受体相关结合蛋白可促进细胞增殖和致瘤性。通过小干扰RNA（siRNA）抑制甘丙肽受体相关结合蛋白表达对CRC细胞SW620产生相反作用的实验进一步证实了这一发现。此外，我们目前的研究表明，细胞周期蛋白D1和β - 连环蛋白的共表达与甘丙肽受体相关结合蛋白表达的改变呈正相关。这些数据表明甘丙肽受体相关结合蛋白在人类CRC的发病机制中起重要作用，并且可能是CRC的一个重要治疗靶点。
Gankyrin, a small and highly conserved protein which is identical to the p28 gene product, was found to be related with the malignant phenotypes in liver and esophageal carcinoma. However, the roles of gankyrin in colorectal carcinoma (CRC) are still unknown. In the present study, the gankyrin mRNA and protein expression in human CRC cell lines and clinical tissue samples were evaluated and correlated with clinicopathological features. Possible mechanisms by which gankyrin regulates the malignant phenotype of CRC cells were also investigated. The results demonstrated that gankyrin was obviously overexpressed in CRC tissues and cell lines compared to controls, and gankyrin expression was correlated with TNM stages and metastasis of CRC. Overexpression of gankyrin by PhkitNeo-hGankyrin plasmid transfected into Lovo cells could promote the cell proliferation and tumorigenicity. This finding was further strengthened by experiments that suppressing gankyrin expression by siRNA exerted the opposite effects on CRC cells SW620. In addition, our present study showed that the co-expression of cyclinD1 and β-catenin were positive correlation with the alteration of gankyrin expression. This data suggested that gankyrin played significant roles in the pathogenesis of human CRC, and might be an important therapeutic target for CRC.