C/EBPα基因第一外显子突变在新疆维吾尔族和汉族宫颈癌发生与发展的作用研究

The prevalence of cervical cancer in Uygur population was greater than that of the Han and other populations. In previous study, we deceted a mutation of 6 bp insertion in the first exon of C/EBP gene, which may be associated with cervical cancer occurrence in Uygur. This project will use the Uygur and Han population to screen this mutation, detect the distribution of the mutation, and analyse its association with cervical cancer and precancerous lesions. The effect of the mutation on the expression of C/EBP gene will be detected by real-time PCR and Western blot. In addition, to detect the infection of HPV16/18, we will analyze the relationship between the mutation and the risk HPV16/18 infection. Additionally, we alse will analyze the effects of the mutation on cell proliferation, apoptosis, invasion and migration of cervical cancer cells. At last, the xenograft tumor model in nude mice will be established to verify the effect of the mutation on the growth of tumor. This study will further reveal the pathogenesis of cervical cancer in Uygur and Han population, and will provide a new molecular marker for the prevention and treatment of cervical cancer.

新疆维吾尔族宫颈癌的患病率明显高于汉族和其他民族，本课题组前期研究在维吾尔族宫颈癌组织中检测出C/EBPα基因第一外显子的一个6个碱基插入突变。本项目将利用维吾尔族和汉族群体对该位点进行筛查，检测突变分布情况，分析其与宫颈癌和癌前病变的相关性。利用实时荧光定量PCR和Western blot检测该突变对C/EBPα基因表达的影响。检测HPV16/18感染情况，分析该突变与高危型HPV16/18感染的关系。利用真核转染实验分析该突变对宫颈癌细胞增殖、凋亡、侵袭、迁移的影响。建立裸鼠异体移植瘤模型，验证该突变对肿瘤生长的作用。本研究将进一步揭示维吾尔族和汉族宫颈癌的发病机制，并有可能为宫颈癌的防治提供新的分子标记。

新疆维吾尔族宫颈癌的患病率明显高于汉族和其他民族，本课题组前期研究在维吾尔族宫颈癌组织中检测出C/EBPα基因第一外显子的一个6个碱基插入突变。该位点的突变可能与维吾尔族宫颈癌的发生有关。本项目利用维吾尔族和汉族群体对该位点进行筛查，检测突变分布情况，实验结果表明该突变不是新疆维吾尔族宫颈组织中特有的突变，在汉族人群中也存在该突变。C/EBPα基因的插入突变在不同损伤程度的宫颈组织中的分布没有差异。通过细胞学实验表明，C/EBPα基因的插入突变可以通过调节细胞周期来抑制宫颈鳞癌细胞的增殖，同时可以抑制宫颈癌细胞的迁移。通过裸鼠移植瘤实验表明，C/EBPα基因的插入突变可以明显抑制肿瘤的生长。综上所述，C/EBPα基因的插入突变是有意义的突变，它有望成为判断宫颈癌预后的一个分子标记。