新基因C16orf72在肿瘤发生中的作用及分子机制

Many potential oncogenes/tumor suppressors were identified previously by our group through screening clinical tumor samples using proteomics technologies. Among them, C16orf72 were found to be significantly down-regulated or silenced in lung cancer, liver cancer, cervix cancer, and so on, but were relatively over-expressed in normal control tissue. Bioinformatic analysis suggest that C16orf72 contain 275 amino acid, and is highly conservative in many vertebrate species. However, the sequence of C16orf72 is not similar with any other gene, and its biology function has not been reported till now. Our further studies indicated that over-expression of C16orf72 can result in apoptosis in many tumor cell lines, and has no noticeable effects on normal cells, indicating it may be a potential tumor suppressor. In the present study, we will perform an investigation on the correlation between the expression level of C16orf72 and tumor genesis and progression. And we will deeply investigated the biology fuction and molecular function of this gene in carcinogenesis in several aspects including interaction proteins, site-specific mutagenesis, and gene overexpression 、gene silence in vivo and vitro studies, with an aim to fill the blank of the function of C16orf72 and provide the theory basis for its further application in clinical diagnosis and therapeutic approach.

前期本课题组利用蛋白质组学等技术筛查了大量临床肿瘤标本，发现了多个潜在癌/抑癌基因。其中C16orf72基因被我们发现在肺癌、肝癌、宫颈癌等恶性肿瘤中缺失或显著低表达，而在相应的正常组织中相对高表达。生物信息学分析表明该基因编码275个氨基酸，在各大物种中高保守，但与现有其他基因序列没有相似性，而其生物学功能目前也尚未见报道。我们进一步的实验研究表明该基因的过表达能够引起多种肿瘤细胞株的凋亡，而对多种正常细胞影响很小，表明C16orf72可能是一个潜在的抑癌基因。本项目拟在前期基础之上，通过临床肿瘤标本分析C16orf72的表达与多种肿瘤发生、发展及预后的相关性，分析其相互作用蛋白、可能的定点突变，并进一步通过基因过表达、基因沉默等多方面在体内外实验深入研究该基因的生物学功能及其在肿瘤发生中的作用，以期在为C16orf72的功能研究填补空白的同时，为其进一步走向临床诊断与治疗提供理论基础。