FLJ22349基因功能的初步研究

发布时间：2018-12-28 21:04

【摘要】： 背景与目的:FLJ22349基因位于染色体22q13.2上,编码一个229个氨基酸的蛋白。生物信息学分析发现多种肿瘤组织中有FLJ22349的表达,预测该基因可能与肿瘤的发生发展有密切关系。本研究旨在用生物信息学方法分析FLJ22349的结构和功能,并初步研究FLJ22349在HEK293及乳腺癌细胞中的作用。方法:运用各种生物信息学数据库初步分析FLJ22349的结构和功能。运用逆转录聚合酶链反应(RT-PCR)方法分析FLJ22349基因在小鼠正常组织,人肿瘤细胞株及人胚肾细胞系HEK293中的表达情况。将载有FLJ22349基因的质粒转染入HEK293,MCF-7,MDA-MB 231中,观察该基因的亚细胞定位,运用MTT方法,检测细胞的生长变化。结果:FLJ22349基因在人类、猩猩、恒河猴、褐家鼠、小鼠和狗中有很高的同源性,但与其它已知的基因无同源性。小鼠正常组织中有FLJ22349表达;乳腺癌细胞株MDA-MB 231,肝癌细胞株Bel-7402也有表达;FLJ22349主要定位于细胞核;转染FLJ22349的HEK293,MCF-7细胞株生长曲线观察到促进细胞生长(P＜0.05)。FLJ22349转染120h后,MTT实验观察到HEK293,MCF-7细胞的增殖率分别为299%,456%;而对照组分别为233%,272%。结论:FLJ22349基因过表达促进HEK293和MCF-7细胞的生长。 [目的]综合评价MDM2(Murine double minute 2)基因启动子309位点多态性与乳腺癌易感性的关系。[方法]检索中国医学文献数据库和PUBMED,以得到MDM2基因SNP309与乳腺癌易感性的关系的病例对照研究,并用meta分析的方法合并SNP309与乳腺癌易感性的关系的OR值。然后进行其中有家族史的乳腺癌亚组分析,敏感性分析和文献的发表偏倚检验。【结果]本次meta分析共纳入10篇文献,乳腺癌家族史组有3篇;累计病例/535例,对照8272例,G等位基因相对于T等位基因OR值为1.01,可信区间0.96-1.06,没有显著性。乳腺癌家族史组G等位基因相对于T等位基因OR值为1.06,可信区间0.94-1.19,没有显著性。[结论]MDM2基因309T＞G多态与乳腺癌易感性没有显著性的关系。
[Abstract]:Background & AIM: FLJ22349 gene is located on chromosome 22q13.2 and encodes a 229 amino acid protein. Bioinformatics analysis showed that FLJ22349 was expressed in many kinds of tumor tissues, and it was predicted that this gene might be closely related to the occurrence and development of tumor. The purpose of this study was to analyze the structure and function of FLJ22349 by bioinformatics and to study the role of FLJ22349 in HEK293 and breast cancer cells. Methods: the structure and function of FLJ22349 were analyzed with various bioinformatics databases. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze the expression of FLJ22349 gene in mouse normal tissue, human tumor cell line and human embryonic kidney cell line HEK293. The plasmid containing FLJ22349 gene was transfected into HEK293,MCF-7,MDA-MB 231. The subcellular localization of the gene was observed and the cell growth was detected by MTT method. Results: FLJ22349 gene had high homology in human, orangutan, rhesus monkey, Rattus norvegicus, mouse and dog, but had no homology with other known genes. FLJ22349 was expressed in normal tissues of mice, MDA-MB 231 in breast cancer cell line and Bel-7402 in hepatoma cell line, FLJ22349 was mainly located in nucleus. The growth curve of HEK293,MCF-7 cell line transfected with FLJ22349 was observed to promote cell growth (P < 0. 05). After 120 hours of FLJ22349 transfection, the proliferation rate of HEK293,MCF-7 cells was observed by MTT assay as 299cells and 456456cells, respectively. In the control group, 2333 and 272 respectively. Conclusion: overexpression of FLJ22349 gene promotes the growth of HEK293 and MCF-7 cells. [objective] to evaluate the association between MDM2 (Murine double minute 2) promoter 309 polymorphism and breast cancer susceptibility. [methods] A case-control study on the relationship between MDM2 gene SNP309 and breast cancer susceptibility was carried out by searching Chinese medical literature database and PUBMED, and the OR value of SNP309 and breast cancer susceptibility was combined with meta analysis. Then the family history of breast cancer subgroup analysis, sensitivity analysis and publication bias test. [results] the meta analysis included 10 articles, breast cancer family history group 3; The OR value of G allele to T allele was 1.01and the confidence interval was 0.96-1.06. there was no significant difference between G allele and T allele. The OR value of G allele to T allele in the family history group of breast cancer was 1.06 and the confidence interval was 0.94-1.19. There was no significant difference between G allele and T allele. [conclusion] MDM2 gene 309T > G polymorphism has no significant relationship with breast cancer susceptibility.
【学位授予单位】：中国协和医科大学
【学位级别】：硕士
【学位授予年份】：2008
【分类号】：R346

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