Silent information regulator 2 （Sir2） proteins, or sirtuins, are nicotine adenine dinucleotide （NAD）-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Si...Silent information regulator 2 （Sir2） proteins, or sirtuins, are nicotine adenine dinucleotide （NAD）-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Sir2 homologs, namely, silent information regulators （SIRT1-7）. SIRT4 and SIRT7 genes play a crucial role in regulating lipid metabolism, cellular growth and metabolism. This suggests that they are potential candidate genes for affecting body size and meat quality traits in animals. Hence, this study aimed to detect genetic variations of both SIRT4 and SIRT7 bovine genes in Qinchuan cattle, and to evaluate the effect of these variations on economically important body size and meat quality traits. Expression analysis using quantitative real-time PCR （qPCR） indicated that SIRT4 and SIRT7 were broadly expressed in all thirteen studied tissues. The expression of SIRT4 was higher in liver, muscle, and in subcutaneous fat tissue. In the case of SIRT7, the expression was higher in lung, abomasum, and subcutaneous fat. Using DNAsequencing, a total of three single nucleotide polymorphisms （SNPs） were identified within SIRT4 and SIRT7 genes in 468 Qinchuan cattle. These included one novel SNP within 3＇ untranslated regions （UTR） of SIRT4 （SNP1： g. 13915A〉G） and two novel synonymous substitutions in SIRT7 （SNP2： g.3587C〉T and SNP3： g.3793T〉C）. Statistical analyses indicated that all three SNPs could significantly influence some body size and meat quality traits in Qinchuan cattle. These novel findings will provide a background for application of bovine SIRT4 and SIRT7 genes in the selection program of Chinese cattle.展开更多
沉默信息调节因子4(silent information regulator 4,SIRT4)是一种依赖NAD~+的蛋白质脱酰酶,主要定位于线粒体,具有ADP-核糖基转移酶、脂酰胺酶、去酰基化酶、去乙酰化酶等活性。近年来研究发现,SIRT4参与线粒体功能调控、氧化应激、炎...沉默信息调节因子4(silent information regulator 4,SIRT4)是一种依赖NAD~+的蛋白质脱酰酶,主要定位于线粒体,具有ADP-核糖基转移酶、脂酰胺酶、去酰基化酶、去乙酰化酶等活性。近年来研究发现,SIRT4参与线粒体功能调控、氧化应激、炎症反应、细胞凋亡等生物学过程的调控,在多种疾病尤其是代谢性疾病的发生发展中发挥重要作用,但其生物学效应与其他线粒体定位的Sirtuins家族成员有所不同,并存在组织特异性。以SIRT4为靶点,开展中药复方及有效单体成分在防治心血管疾病、肿瘤、糖尿病、老年病中的机制研究日益受到关注。本文总结了SIRT4的酶活性和生物学功能,并归纳了其在相关疾病中的作用及中医药调控的研究进展,希望能够为新药开发、临床转化提供新思路。展开更多
文摘目的探究miRNA-424-5p(miR-424-5p)调控SIRT4表达影响胃癌细胞迁移和侵袭能力的潜在分子机制。方法利用RT-qPCR检测57例胃癌患者肿瘤组织与癌旁组织中miR-424-5p和SIRT4的表达水平。用脂质体法将miR-424-5p inhibitor和miR-424-5p mimic分别瞬时转染入MNK-28和HGC-27胃癌细胞中,RT-qPCR检测细胞中miR-424-5p和SIRT4 mRNA的表达水平,Western Blot检测细胞中SIRT4蛋白的表达量,划痕愈合实验和Transwell侵袭实验检测各组细胞的迁移和侵袭能力。双荧光素酶基因报告实验检测miR-424-5p对SIRT4的靶向调控机制。共转染miR-424-5p和SIRT4进一步验证miR-424-5p和SIRT4对胃癌细胞迁移和侵袭能力的影响。结果胃癌组织中miR-424-5p的表达明显高于癌旁组织(P<0.001),SIRT4的表达水平明显低于癌旁组织(P<0.001),相关性分析表明胃癌组织中miR-424-5p的表达与SIRT4呈负相关(r=-0.382,P=0.034)。此外,miR-424-5p高表达与肿瘤的浸润深度、TNM分期、脉管侵犯和神经侵犯显著相关(均P<0.05)。过表达miR-424-5p能促进胃癌细胞迁移和侵袭能力,而抑制miR-424-5p表达则呈现出相反的效果。过表达miR-424-5p可降低胃癌细胞中SIRT4 m RNA和蛋白的表达水平,相反,抑制miR-424-5p表达则上调胃癌细胞中SIRT4 m RNA和蛋白的表达水平。双荧光素酶报告基因实验显示miR-424-5p能显著影响野生型SIRT4-3’UTR表达载体的荧光素酶活性。回复实验结果显示miR-424-5p和SIRT4能显著影响胃癌细胞的迁移和侵袭能力。结论miR-424-5p在胃癌中高表达,其通过靶向抑制抑癌基因SIRT4的表达促进肿瘤细胞的迁移和侵袭,从而参与胃癌的的发生、发展。
基金supported by the National 863 Program of China (2013 AA102505)the National Natural Science Foundation of China (31272411 and 31402044)+2 种基金the National Beef and Yak Industrial Technology System,China (CARS-38)the China Postdoctoral Science Foundation (2016M590976)the Key Technologies R&D Program of Henan Province,China (122102110062)
文摘Silent information regulator 2 （Sir2） proteins, or sirtuins, are nicotine adenine dinucleotide （NAD）-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Sir2 homologs, namely, silent information regulators （SIRT1-7）. SIRT4 and SIRT7 genes play a crucial role in regulating lipid metabolism, cellular growth and metabolism. This suggests that they are potential candidate genes for affecting body size and meat quality traits in animals. Hence, this study aimed to detect genetic variations of both SIRT4 and SIRT7 bovine genes in Qinchuan cattle, and to evaluate the effect of these variations on economically important body size and meat quality traits. Expression analysis using quantitative real-time PCR （qPCR） indicated that SIRT4 and SIRT7 were broadly expressed in all thirteen studied tissues. The expression of SIRT4 was higher in liver, muscle, and in subcutaneous fat tissue. In the case of SIRT7, the expression was higher in lung, abomasum, and subcutaneous fat. Using DNAsequencing, a total of three single nucleotide polymorphisms （SNPs） were identified within SIRT4 and SIRT7 genes in 468 Qinchuan cattle. These included one novel SNP within 3＇ untranslated regions （UTR） of SIRT4 （SNP1： g. 13915A〉G） and two novel synonymous substitutions in SIRT7 （SNP2： g.3587C〉T and SNP3： g.3793T〉C）. Statistical analyses indicated that all three SNPs could significantly influence some body size and meat quality traits in Qinchuan cattle. These novel findings will provide a background for application of bovine SIRT4 and SIRT7 genes in the selection program of Chinese cattle.
文摘沉默信息调节因子4(silent information regulator 4,SIRT4)是一种依赖NAD~+的蛋白质脱酰酶,主要定位于线粒体,具有ADP-核糖基转移酶、脂酰胺酶、去酰基化酶、去乙酰化酶等活性。近年来研究发现,SIRT4参与线粒体功能调控、氧化应激、炎症反应、细胞凋亡等生物学过程的调控,在多种疾病尤其是代谢性疾病的发生发展中发挥重要作用,但其生物学效应与其他线粒体定位的Sirtuins家族成员有所不同,并存在组织特异性。以SIRT4为靶点,开展中药复方及有效单体成分在防治心血管疾病、肿瘤、糖尿病、老年病中的机制研究日益受到关注。本文总结了SIRT4的酶活性和生物学功能,并归纳了其在相关疾病中的作用及中医药调控的研究进展,希望能够为新药开发、临床转化提供新思路。
