目的:皮肤的发生发育及损伤修复受到各种生长因子和细胞因子的综合调控。p63是近年发现的癌基因p53的同源基因,研究证实,p63在发育和肿瘤发生中都具有重要作用。文章对p63在皮肤发生发育和损伤修复中的作用及其研究进展作一综述。资料来...目的:皮肤的发生发育及损伤修复受到各种生长因子和细胞因子的综合调控。p63是近年发现的癌基因p53的同源基因,研究证实,p63在发育和肿瘤发生中都具有重要作用。文章对p63在皮肤发生发育和损伤修复中的作用及其研究进展作一综述。资料来源:应用计算机检索Pubmed数据库1999-01/2007-08期间的相关文章,检索词"p63,skin or cutis,development,epidermal ste m cells,healing or repair",限定文章语言种类为English。同时计算机检索中国期刊全文数据库、万方数据库1999-01/2007-08期间的相关文章,检索词"p63,皮肤,发生发育,表皮干细胞,修复",限定文章语言种类为中文。资料选择:对资料进行初审,选取符合研究要求的有关文章并查看每篇文献后的引文。纳入标准:有关p63在皮肤发生发育中作用的研究;有关p63在皮肤损伤修复中作用的研究。排除标准:重复或类似的研究、综述文献。资料提炼:共收集到61篇相关文献,28篇文献符合纳入标准,排除的33篇重复或类似的研究文献,其中25篇为p63与皮肤发生发育相关的研究,3篇为p63与皮肤创伤修复方面的研究。资料综合:①p63与皮肤发生发育相关的研究:p63为胚胎发育过程中最初上皮分层所必需,单层体表外胚层上皮层化的程序发动和执行需要不同p63异构体的有序激活,p63的异构体蛋白均来自于同一个基因,由于在转录水平有不同的启动子参与和剪切的不同形成,不同的异构体蛋白作用不同并有相互作用;p63可能激活人类角质形成细胞中的各种分化基因启动子,从而最终调控角质细胞的分化方向;p63基因在角质形成细胞增殖和凋亡过程中具有重要的平衡作用;p63在发育过程中的主要作用在于促使外胚层分化和增生;p63在成熟上皮中维持表皮干细胞的潜在增殖力,是首个能明确将表皮干细胞同短暂扩充细胞区别的基因。②p63与皮肤创伤修复方面的研究:p63在皮肤的发育和损伤愈合中时间上有规律,部位上有选择性地表达;p63是皮肤损伤修复过程中高增殖潜能角质形成细胞的标志并对皮肤损伤病理进程进行调控。结论:p63为胚胎发育过程中最初的上皮分层所必需,在成熟上皮中有维持表皮干细胞的潜在增殖力的作用,是皮肤损伤修复过程中高增殖潜能角质形成细胞的标志并对皮肤损伤病理进程进行调控。展开更多
Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of no...Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of non-coding RNAs,microRNAs(miRNAs) in cancer development,with several conjectures regarding their possible involvement in the evolution of drug resistance.This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer.The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line(OV2008) and its resistant variant(C13*) was identified by real-time PCR.An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry,were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells.Real-time PCR,Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b.As compared with OV2008 cells,the expression levels of miR-125b in C13* cells were increased.It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells.Moreover,Bak1 was a direct target of miR-125b,and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin.Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression.This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.展开更多
文摘目的:皮肤的发生发育及损伤修复受到各种生长因子和细胞因子的综合调控。p63是近年发现的癌基因p53的同源基因,研究证实,p63在发育和肿瘤发生中都具有重要作用。文章对p63在皮肤发生发育和损伤修复中的作用及其研究进展作一综述。资料来源:应用计算机检索Pubmed数据库1999-01/2007-08期间的相关文章,检索词"p63,skin or cutis,development,epidermal ste m cells,healing or repair",限定文章语言种类为English。同时计算机检索中国期刊全文数据库、万方数据库1999-01/2007-08期间的相关文章,检索词"p63,皮肤,发生发育,表皮干细胞,修复",限定文章语言种类为中文。资料选择:对资料进行初审,选取符合研究要求的有关文章并查看每篇文献后的引文。纳入标准:有关p63在皮肤发生发育中作用的研究;有关p63在皮肤损伤修复中作用的研究。排除标准:重复或类似的研究、综述文献。资料提炼:共收集到61篇相关文献,28篇文献符合纳入标准,排除的33篇重复或类似的研究文献,其中25篇为p63与皮肤发生发育相关的研究,3篇为p63与皮肤创伤修复方面的研究。资料综合:①p63与皮肤发生发育相关的研究:p63为胚胎发育过程中最初上皮分层所必需,单层体表外胚层上皮层化的程序发动和执行需要不同p63异构体的有序激活,p63的异构体蛋白均来自于同一个基因,由于在转录水平有不同的启动子参与和剪切的不同形成,不同的异构体蛋白作用不同并有相互作用;p63可能激活人类角质形成细胞中的各种分化基因启动子,从而最终调控角质细胞的分化方向;p63基因在角质形成细胞增殖和凋亡过程中具有重要的平衡作用;p63在发育过程中的主要作用在于促使外胚层分化和增生;p63在成熟上皮中维持表皮干细胞的潜在增殖力,是首个能明确将表皮干细胞同短暂扩充细胞区别的基因。②p63与皮肤创伤修复方面的研究:p63在皮肤的发育和损伤愈合中时间上有规律,部位上有选择性地表达;p63是皮肤损伤修复过程中高增殖潜能角质形成细胞的标志并对皮肤损伤病理进程进行调控。结论:p63为胚胎发育过程中最初的上皮分层所必需,在成熟上皮中有维持表皮干细胞的潜在增殖力的作用,是皮肤损伤修复过程中高增殖潜能角质形成细胞的标志并对皮肤损伤病理进程进行调控。
基金supported by grants from the National Natural Sciences Foundation of China (No.81001153)the "973" Program of China (No. 2009CB521808)
文摘Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a successful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of non-coding RNAs,microRNAs(miRNAs) in cancer development,with several conjectures regarding their possible involvement in the evolution of drug resistance.This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer.The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line(OV2008) and its resistant variant(C13*) was identified by real-time PCR.An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry,were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells.Real-time PCR,Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b.As compared with OV2008 cells,the expression levels of miR-125b in C13* cells were increased.It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells.Moreover,Bak1 was a direct target of miR-125b,and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin.Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression.This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.
