The tumor-promoting function of ECRG4 in papillary thyroid carcinoma and its related mechanism
The tumor-promoting function of ECRG4 in papillary thyroid carcinoma and its related mechanism
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ECRG4在甲状腺乳头状癌中的促癌作用及其相关机制
DOI：
10.1007/s13277-014-2731-1
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发表时间：
2015-02-01
期刊：
影响因子：
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通讯作者：
Zhang, Wei
中科院分区：
文献类型：
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作者：
Chen, Jiayu;Liu, Chibo;Zhang, Wei
本研究旨在探讨食管癌相关基因4（ECRG 4）在甲状腺乳头状癌中的促癌作用及其相关机制。采用实时定量PCR（Q-RT-PCR）、Western blot和免疫组化方法检测甲状腺乳头状癌组织中ECRG 4 mRNA和蛋白的表达。采用亚硫酸氢盐测序法对10对甲状腺乳头状癌患者的新鲜标本进行ECRG 4启动子CpG岛甲基化状态分析。我们还用慢病毒将ECRG 4转染到甲状腺乳头状癌细胞系W3和K1中，通过检测这些转化细胞的增殖活性、细胞周期和细胞凋亡率的变化来分析ECRG 4的功能。我们发现，ECRG 4的表达上调，在大多数乳头状甲状腺癌样本（70.0%，28 40乳头状甲状腺癌样本）的蛋白质水平上，ECRG 4的mRNA水平也增强肿瘤组织相比，其匹配的非肿瘤组织。ECRG 4启动子区域周围的CpG岛在甲状腺乳头状癌样本中被去甲基化。同时，ECRG 4在甲状腺乳头状癌细胞系W3和K1中的表达上调，可促进细胞增殖活性和细胞周期由G1期向G2期的转变，但不影响细胞凋亡率。ECRG 4在甲状腺乳头状癌中的表达经常通过基因启动子区CpG岛的去甲基化机制上调，并且ECRG 4通过诱导甲状腺乳头状癌细胞从G1期向G2期的细胞周期转变而具有促肿瘤作用。
This study aimed to explore the tumor-promoting function of esophageal cancer-related gene 4 (ECRG4) in the papillary thyroid cancer and its related mechanism. ECRG4 Messenger RNA (mRNA) and protein expression analysis in papillary thyroid cancer tissues was performed by quantitative real-time PCR (Q-RT-PCR), Western blot, and immunohistochemistry methods. Ten pairs of fresh samples from the papillary thyroid carcinoma patients were analyzed for ECRG4 promoter CpG island methylation status by bisulfite sequencing analysis. We also transfected ECRG4 into papillary thyroid cancer cell lines W3 and K1 with lentivirus and analyzed ECRG4 functions through evaluating the changes of the proliferation activity, the cell cycle, and the cell apoptosis rate of these transformed cells. We found that ECRG4 expression was upregulated in most papillary thyroid cancer samples (70.0 %, 28 out of 40 papillary thyroid cancer samples) on the protein level, and the ECRG4 mRNA level was also enhanced in tumor tissues compared to their matched nontumor tissues. CpG islands around the ECRG4 promoter region were demethylated in the papillary thyroid cancer samples. At the same time, the upregulated expression of ECRG4 in papillary thyroid cancer cell lines W3 and K1 could promote both the proliferation activity and the cell cycle transition from the G1 phase into the G2 but could not affect the cell apoptosis rate. The expression of ECRG4 is frequently upregulated in a papillary thyroid carcinoma through the demethylation mechanism of CpG islands in the gene promoter region, and the ECRG4 has a tumor-promoting function through inducing the cell cycle transition from the G1 phase to the G2 in papillary thyroid carcinoma cells.