中文摘要：

背景与目的：LRP16基因是新发现的白血病相关基因,其生物学功能还远未被阐明。本研究基于生物信息学分析探讨人类LRP16基因的生物学功能。方法：采用生物信息学方法分析LRP16基因启动子及编码蛋白的结构、功能,并对预测结果进行实验验证。建立pGL3-Basic重组载体,并进行荧光素酶活性分析。构建ORF-pcDNA3.1＋真核表达载体,转染入HL-60、K562细胞后,采用单细胞凝胶电泳法检测HL-60细胞紫外线损伤,流式细胞术检测K562细胞周期。结果：LRP16基因启动子是一个典型的Ⅱ型真核启动子,核心调控区位于-600bp以内,具有7个与细胞周期、造血调控、细胞增殖及DNA损伤修复等有关的顺式作用元件。LRP16基因长型编码蛋白在148～315氨基酸残基之间具有与人类组蛋白H2A1C末端相类似的同源序列hismacro、COG2110和A1pp。紫外线照射HL-60细胞后,LRP16过表达组的彗星细胞数量、慧尾长度明显小于空质粒对照组,且活细胞数量明显多于空质粒对照组。过表达LRP16基因的K562细胞的增殖速度和G2/M期、S期细胞均明显高于空质粒对照组,且提前达到平台期。结论：基于生物信息学方法分析表明LRPl6基因具有促进白血病细胞增殖、调控细胞周期及抗紫外线的DNA损伤作用。

英文摘要：

Background and Objective： LRP16 is a human novel gene linked to leukemia identified recently. However, its biological function is not fully clarified so far. This study was to investigate the biological function of human LRP16 gene by database-aided bioinformatics analysis, Methods. The structures and functions of LRP16 gene promoter and its coding protein were analyzed using bioinformatics prediction, and further experimental testing was performed. The recombinants of pGL3-basic and LRP16 promoter subclones were constructed for luciferase activity analysis. The recombinant of LRP16 open reading frame coding sequence and pcDNA3.1 eukaryotic expression vector was established and transfected into HL-60 and K562 cell lines. DNA damage of HL-60 cells after ultraviolet irradiation was evaluated using single cell gel electrophoresis. Cell cycle of K562 cells was analyzed by flow cytometry. Results： LRP16 promoter was a typical class II eukaryotic promoter and its core regulation sequence was located within upstream -600 bp of transcriptional start site. In addition, seven cis-acting elements, which may be implicated in cell cycle, hematopoiesis regulation, cell proliferation and repair of DNA damage, were identified. Long type LRP16 coding protein contained homologous sequences of hismacro, COG2110, and Alpp with human histone H2A1C between 148 and 315 amino acid residue. The number of comet cells and the length of comet tail in HL-60 cells irradiated were significantly decreased and the number of living cell was significantly increased in LRP16-overexpression group compared with empty plasmid control group. The proliferation rate and ratio or quantity of GJM and S phases were significantly increased in LRP16-overexpression K562 group compared with empty plasmid control group. LRP16-overexpression in K562 cells promoted the transition of G1 to S phase and plateau phase of cell proliferation was advanced. Conclusions： Promoter regulation prediction and protein domain analysis based on bioinformatics contribute to