Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer
Klotho, an anti-senescence related gene, is frequently inactivated through promoter hypermethylation in colorectal cancer
复制标题
Klotho 是一种抗衰老相关基因，在结直肠癌中经常通过启动子高甲基化而失活
DOI：
10.1007/s13277-011-0174-5
复制
发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Wang, Liang Jing
中科院分区：
文献类型：
--
作者：
Pan, Jie;Zhong, Jing;Wang, Liang Jing
潜在的抗衰老基因Klotho（KL）最近被发现参与几种不同人类癌症的进展，包括乳腺癌、肺癌和宫颈癌。在这项研究中，我们确定KL作为一个候选的肿瘤抑制基因沉默通过启动子高甲基化在结直肠癌（CRC）。在结肠癌细胞系中发现KL基因表达缺失或降低（5/6，83.3%），其可被去甲基化剂5-氮杂-2 ′-脱氧胞苷（Aza）逆转，但不能被HDAC抑制剂阿司他汀A逆转。此外，KL在大肠癌组织中的表达与癌旁组织相比显著下调（n= 25，p< 0.001）。KL基因启动子甲基化在原发性结肠癌组织中的检出率为85%（34/40），而在癌旁结肠组织中的检出率为85%（34/40）。此外，KL的异位表达通过诱导细胞凋亡和S期细胞周期阻滞导致结肠癌细胞系的细胞增殖抑制。综上所述，我们的研究结果表明KL是通过启动子超甲基化失活的，并可能在结直肠癌中作为抑癌基因发挥作用。
The potential anti-senescence gene Klotho (KL) has been recently found to participate in the progression of several different human cancers including breast, lung, and cervical cancer. In this current study, we identified KL as a candidate tumor suppressor gene silenced through promoter hypermethylation in colorectal cancer (CRC). KL gene expression is found to be absent or reduced in colon cancer cell lines (5/6, 83.3%), which can be reversed by treatment with demethylation agent 5-aza-2′-deoxycytidine (Aza), but not HDAC inhibitor trichostatin A. In addition, KL expression is markedly downregulated in colorectal carcinoma tissues when compared to the adjacent nontumor tissues (n= 25,p< 0.001). The methylation of the KL gene promoter was frequently detected in primary tumor tissues (34/40, 85%) when compared with adjacent nontumor colon tissues. Furthermore, ectopic expression of KL led to the cell proliferation inhibition of colon cancer cell lines via the induction of cell apoptosis and S-phase cell cycle arrest. Taken together, our results suggest that KL is inactivated through promoter hypermethylation and potentially functions as a tumor suppressor gene in CRC.