hClock gene expression in human colorectal carcinoma
hClock gene expression in human colorectal carcinoma
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hClock基因在人结直肠癌中的表达
DOI：
10.3892/mmr.2013.1643
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发表时间：
2013-10-01
影响因子：
3.4
通讯作者：
Hua, Luchun
中科院分区：
文献类型：
--
作者：
Wang, Liying;Chen, Bozan;Hua, Luchun
在这项研究中，我们的目的是研究在大肠癌（CRC）中，人类时钟（hClock），在昼夜节律基因家族的核心基因的表达的变化，并讨论可能的影响。先前的研究表明，昼夜节律的破坏是导致CRC启动和发展的内源性因素之一。然而，与CRC相关的昼夜节律基因的潜在分子变化尚未被探索。应用免疫荧光和定量聚合酶链反应（qPCR）技术检测30例大肠癌组织中hCLOCK蛋白和基因的表达。hCLOCK蛋白在从30例CRC患者获得的所有标本中表达。与配对的非癌组织相比，在人类CRC组织中观察到更高水平的hCLOCK表达。hCLOCK表达在低分化或晚期Dukes分级肿瘤和64.3%有淋巴结转移的肿瘤病例中显著较高。hClock基因在所有标本中均有表达。与配对的非癌组织相比，在人类CRC病例中发现hClock的表达显著更高。人CRCs中hClock基因表达与蛋白表达之间存在强的正线性相关。在人CRCs中hClock基因表达与ARNT、HIF-1 α和VEGF表达之间也发现了强的正线性相关。hClock与巴克、Bax、Bid、肿瘤坏死因子受体I（TNFR I）和TNFR II无明显相关性。昼夜节律基因hClock在人大肠黏膜中稳定表达，对调控下游生物钟调控基因的表达具有重要意义。hCLOCK可能与HIF-1 α/ARNT相互作用，激活VEGF，刺激肿瘤血管生成和转移。
In this study, we aimed to investigate changes in the expression of human Clock (hClock), a gene at the core of the circadian gene family, in colorectal carcinomas (CRCs) and to discuss the possible effects. Previous studies have revealed that the disruption of circadian rhythms is one of the endogenous factors that contribute to the initiation and development of CRCs. However, the underlying molecular changes to the circadian genes associated with CRCs have not been explored. Immunofluorescence and quantitative polymerase chain reaction (qPCR) analysis of the hCLOCK protein and gene expression were performed in 30 cases of CRC. The hCLOCK protein was expressed in all specimens obtained from 30 CRC patients. Higher levels of hCLOCK expression were observed in human CRC tissues compared with the paired non-cancerous tissues. hCLOCK expression was significantly higher in poorly differentiated, or late-stage, Dukes' grade tumors and in 64.3% of tumor cases with lymph node metastasis. The hClock gene was expressed in all specimens. A significantly higher expression of hClock was found in human CRC cases compared with paired non-cancerous tissues. There was a strong positive linear correlation between hClock gene expression and protein expression in human CRCs. A strong positive linear correlation was also found between hClock gene expression and ARNT, HIF-1 alpha and VEGF expression in human CRCs. There was no significant correlation between hClock and Bak, Bax, Bid, tumor necrosis factor receptor I (TNFR I) and TNFR II. The circadian gene hClock was stably expressed in human colorectal mucosa and was important in regulating the expression of downstream clock-controlled genes. hCLOCK may interact with HIF-1 alpha/ARNT and activate VEGF to stimulate tumor angiogenesis and metastasis.