为了探究脂肪量和肥胖相关(fat mass and obesity associated,FTO)基因多态性及其对鸡屠体性状和生长性状的影响,试验采用DNA测序检测鸡FTO基因编码区的单核苷酸多态性(SNP),并采用一般线性模型中的LSD法分析FTO基因多态性对和盈黑鸡屠...为了探究脂肪量和肥胖相关(fat mass and obesity associated,FTO)基因多态性及其对鸡屠体性状和生长性状的影响,试验采用DNA测序检测鸡FTO基因编码区的单核苷酸多态性(SNP),并采用一般线性模型中的LSD法分析FTO基因多态性对和盈黑鸡屠体性状和生长性状的影响。结果表明:在FTO基因第5外显子和第7外显子上各检测到一个SNP位点,分别为g.57337C>A和g.64757T>G突变。g.57337C>A突变形成AA、AB和BB 3种基因型,g.64757T>G突变形成TT、TG和GG 3种基因型。g.57337C>A位点对和盈黑鸡屠体重、宰前活重、头重、胸肌重、腿肌重上、肝脏重、心脏重7个屠体性状有显著或极显著影响(P<0.05或P<0.01),对8,10,16周龄体重影响显著(P<0.05)。g.64757T>G位点对和盈黑鸡宰前活重、全净膛重、半净膛重、屠体重和翅重5个屠体性状有显著影响(P<0.05),对16周龄体重影响显著(P<0.05)。说明FTO基因g.57337C>A和g.64757T>G位点可作为和盈黑鸡屠体性状和生长性状遗传改良的重要候选分子标记。展开更多
6-甲基腺嘌呤(N6-methyladenosine,m6A)甲基化修饰是真核生物中最常见的mRNA甲基化修饰之一,影响mRNA的剪接、翻译、稳定、降解等过程。肥胖相关蛋白(fat mass and obesity-associated protein,FTO)作为第一个被发现的m6A去甲基化酶,在...6-甲基腺嘌呤(N6-methyladenosine,m6A)甲基化修饰是真核生物中最常见的mRNA甲基化修饰之一,影响mRNA的剪接、翻译、稳定、降解等过程。肥胖相关蛋白(fat mass and obesity-associated protein,FTO)作为第一个被发现的m6A去甲基化酶,在肿瘤增殖、迁移、侵袭、耐药、肿瘤微环境及代谢重编程方面发挥重要作用。本文就m6A去甲基化酶FTO在恶性肿瘤中的调控作用及作用机制的研究进展进行综述。展开更多
In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers a...In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO expression.Application of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative splicing.Overexpression of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle assembly.These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.展开更多
Background:Osteosarcoma(OS),recognized as the predominant malignant tumor originating from bones,necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance tre...Background:Osteosarcoma(OS),recognized as the predominant malignant tumor originating from bones,necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance treatment methodologies.The role of fat mass and obesity-associated(FTO)in OS,particularly its correlation with malignant traits,and the fundamental mechanism,remains to be elucidated.Materials and Methods:1.The FTO expression and survival rate in tumors were analyzed.2.FTO in OS cell lines was quantified utilizing western blot and PCR.3.FTO was upregulated and downregulated separately in MG63.4.The impact of FTO on the proliferation and migration of OS cells was evaluated using CCK-8,colony formation,wound healing,and Transwell assays.5.The expression of miR-150-5p in OS cells-derived exosomes was identified.6.The binding of miR-150-5p to FTO was predicted by TargetScan and confirmed by luciferase reporter assay.7.The impact of exosome miR-150-5p on the proliferation and migration of OS cells was investigated.Results:The expression of FTO was higher in OS tissues compared to normal tissues correlating with a worse survival rate.Furthermore,the downregulation of FTO significantly impeded the growth and metastasis of OS cells.Additionally,miR-150-5p,which was downregulated in both OS cells and their derived exosomes,was found to bind to the 3′-UTR of FTO through dual luciferase experiments.Exosomal miR-150-5p was found to decrease the expression of FTO and inhibit cell viability.Conclusions:We identified elevated levels of FTO in OS,which may be attributed to insufficient miR-150-5p levels in both the cells and exosomes.It suggests that the dysregulation of miR-150-5p and its interaction with FTO could potentially promote the development of OS.展开更多
Dear Editor,Genome-wide association studies(GWAS)revealed a large number of common variants in the human genome associated with an increased risk of diseases.The lead signals of common obesity-associated variants are ...Dear Editor,Genome-wide association studies(GWAS)revealed a large number of common variants in the human genome associated with an increased risk of diseases.The lead signals of common obesity-associated variants are located within the first intron of the FTO(fat mass and obesity-associated)gene,being the most significant and impactive single-nucleotide polymorphism(SNP)clusters in obesity inheritance[1].Although a strong positive association between these FTO“risk SNPs”(including rs1421085 T>C)and obesity is reported across human populations of diverse ancestry,relatively weak(even none)significant associations have been observed in African populations[2].As known,the frequency of the FTO SNPs varies among different ancestral groups,with the“risk allele”being prevalent in individuals of European ancestry and less common in Asian and African populations.Notably,the linkage disequilibrium(LD)of the“risk SNPs”in African populations was much lower than in non-African populations[3].The reason for the discrepancy remains elusive thus far;however,it could be redefined in the context of the unexpected biological function of the FTO SNPs in vivo[4].展开更多
为了探究绵羊FTO(Fat mass and obesity-associated protein)基因的结构和功能,试验采用绵羊皮肤组织RNA-seq获得的CDS序列和生物信息学方法对FTO基因的核苷酸序列的相似性、氨基酸序列、蛋白理化性质、蛋白二、三级结构、亚细胞定位和...为了探究绵羊FTO(Fat mass and obesity-associated protein)基因的结构和功能,试验采用绵羊皮肤组织RNA-seq获得的CDS序列和生物信息学方法对FTO基因的核苷酸序列的相似性、氨基酸序列、蛋白理化性质、蛋白二、三级结构、亚细胞定位和互作蛋白进行研究。结果表明,绵羊FTO基因CDS区为1518 bp,共编码505个氨基酸,其中亮氨酸(Leu)含量最多(11.1%),组氨酸(His)含量最少(2.6%);FTO蛋白分子式C_(2609)H_(4053)N_(709)O_(771)S_(27),分子的质量为58553.79,理论等电点(pI)为5.28,半衰期为30h,结构不稳定,属于亲水性蛋白,不具有信号肽和跨膜结构域;FTO主要分布在细胞外基质中;多肽链中含有43.17%α螺旋结构、38.61%无规则卷曲、11.49%延伸链和6.73%β折叠结构;FTO与FOXO1、CREB1、ALKBH8、ALKBH5、YTHDF1、YTHDF3、YTHDF2、METTL14、WTAP、METTL310个蛋白可能存在互作。说明绵羊的FTO蛋白主要与RNA甲基化调控相关蛋白互作,为进一步研究其功能提供参考。展开更多
为了明确肉质相关基因氟烷基因(Hal)、酸肉基因(RN)和脂肪肥胖相关基因(FTO)在国内外不同猪种群体间的遗传变异特性,本研究以大约克、长白、杜洛克和金华猪等猪种群体为研究对象,应用PCR-RFLP技术分别检测了Hal、RN和FTO基因的多态性,...为了明确肉质相关基因氟烷基因(Hal)、酸肉基因(RN)和脂肪肥胖相关基因(FTO)在国内外不同猪种群体间的遗传变异特性,本研究以大约克、长白、杜洛克和金华猪等猪种群体为研究对象,应用PCR-RFLP技术分别检测了Hal、RN和FTO基因的多态性,并分析了FTO基因上2个多态位点g.276G>T和c.594C>G的遗传变异情况。结果表明:(1)在杜洛克猪中发现了Hal的基因型Hal NHal n,其频率为0.166,但未发现基因型Hal n Hal n,其它猪种群体中仅检测到了基因型Hal NHal N;(2)在已检测的所有猪种群体中只检测到RN基因的rn/rn基因型,未发现rn/RN和RN/RN基因型;(3)在FTO的g.276G>T位点上,金华猪呈现单态,其它猪种群体均呈现多态。在FTO的c.594C>G位点上,4个猪种群体均呈现多态,3个外来猪种群体均以CC基因型频率较高,而金华猪则以GG基因型频率较高。研究结果提示,由于Hal基因在养猪生产中的利弊双重性,因此在某些猪种群体中仍然存在较高频率的Hal NHal n基因型。此外,结合FTO基因的生理功能和已有的研究结果,可在特定的猪群中将其作为影响猪肉质性状的候选基因。本研究发现FTO的基因型分布在我国优良地方猪种金华猪与国外3个种猪群间存在较大差异,为深入研究不同品种猪的肉质形成机理提供了基础数据。展开更多
目的:FTO(fat-mass and obesity-associated)基因是首个得以广泛验证的肥胖易感基因,FTO rs9939609位点的突变与肥胖和糖尿病等密切相关。以男大学生为例,探讨运动和饮食干预对于FTO不同基因型个体影响的差异。方法:将被试随机分为运动...目的:FTO(fat-mass and obesity-associated)基因是首个得以广泛验证的肥胖易感基因,FTO rs9939609位点的突变与肥胖和糖尿病等密切相关。以男大学生为例,探讨运动和饮食干预对于FTO不同基因型个体影响的差异。方法:将被试随机分为运动组(E组)、运动饮食控制组(E+D组)、对照组(C组),运动类型主要为有氧运动,饮食干预主要包括营养知识讲座和反馈。检测所有被试FTO rs9939609位点基因型,测试指标主要为体成分和糖尿病相关指标。结果:对于FTO rs9939609位点TT型,E组在干预后BMI和体脂百分比的下降程度显著性高于C组,E+D组BMI、体脂百分比、内脏脂肪指数和血糖的下降程度显著性高于C组;而对于FTO rs9939609位点TA型被试,E+D组BMI、腰围和体脂百分比、血糖的下降程度显著高于C组。运动饮食干预对于风险等位基因携带者腰围的干预效果更明显。结论:运动和饮食干预显著改善被试体成分和血糖等指标。运动饮食干预对于携带FTO风险等位基因的TA型被试腰围干预效果更明显。展开更多
文摘为了探究脂肪量和肥胖相关(fat mass and obesity associated,FTO)基因多态性及其对鸡屠体性状和生长性状的影响,试验采用DNA测序检测鸡FTO基因编码区的单核苷酸多态性(SNP),并采用一般线性模型中的LSD法分析FTO基因多态性对和盈黑鸡屠体性状和生长性状的影响。结果表明:在FTO基因第5外显子和第7外显子上各检测到一个SNP位点,分别为g.57337C>A和g.64757T>G突变。g.57337C>A突变形成AA、AB和BB 3种基因型,g.64757T>G突变形成TT、TG和GG 3种基因型。g.57337C>A位点对和盈黑鸡屠体重、宰前活重、头重、胸肌重、腿肌重上、肝脏重、心脏重7个屠体性状有显著或极显著影响(P<0.05或P<0.01),对8,10,16周龄体重影响显著(P<0.05)。g.64757T>G位点对和盈黑鸡宰前活重、全净膛重、半净膛重、屠体重和翅重5个屠体性状有显著影响(P<0.05),对16周龄体重影响显著(P<0.05)。说明FTO基因g.57337C>A和g.64757T>G位点可作为和盈黑鸡屠体性状和生长性状遗传改良的重要候选分子标记。
文摘6-甲基腺嘌呤(N6-methyladenosine,m6A)甲基化修饰是真核生物中最常见的mRNA甲基化修饰之一,影响mRNA的剪接、翻译、稳定、降解等过程。肥胖相关蛋白(fat mass and obesity-associated protein,FTO)作为第一个被发现的m6A去甲基化酶,在肿瘤增殖、迁移、侵袭、耐药、肿瘤微环境及代谢重编程方面发挥重要作用。本文就m6A去甲基化酶FTO在恶性肿瘤中的调控作用及作用机制的研究进展进行综述。
基金supported by the Natural Science Foundation of Shandong Province,China (ZR2017MC033)National Key Research and Development Program of China (2023YFD1300504)Taishan Scholar Construction Foundation of Shandong Province,China (ts20190946)。
文摘In eukaryotic organisms,the most common internal modification of messenger RNA(m RNA)is N6-methyladenosine(m6A).This modification can be dynamically and reversibly controlled by specific enzymes known as m6A writers and erasers.The fat-mass and obesity-associated protein(FTO)catalyzes RNA demethylation and plays a critical role in various physiological and pathological processes.Our research identified dynamic alterations in both m6A and FTO during the assembly of primordial follicles,with an inverse relationship observed for m6A levels and nuclear-localized FTO expression.Application of Fto small interfering RNA(si RNA)altered the expression of genes related to cell proliferation,hormone regulation,and cell chemotaxis,and affected RNA alternative splicing.Overexpression of the full-length Fto gene led to changes in m6A levels,alternative splicing of Cdk5,cell proliferation,cell cycle progression,and proportion of primordial follicles.Conversely,overexpression of Fto lacking a nuclear localization signal(NLS)did not significantly alter m6A levels or primordial follicle assembly.These findings suggest that FTO,localized in the nucleus but not in the cytoplasm,regulates RNA m6A demethylation and plays a role in cell proliferation,cell cycle progression,and primordial follicle assembly.These results highlight the potential of m6A and its eraser FTO as possible biomarkers and therapeutic targets.
文摘Background:Osteosarcoma(OS),recognized as the predominant malignant tumor originating from bones,necessitates an in-depth comprehension of its intrinsic mechanisms to pinpoint novel therapeutic targets and enhance treatment methodologies.The role of fat mass and obesity-associated(FTO)in OS,particularly its correlation with malignant traits,and the fundamental mechanism,remains to be elucidated.Materials and Methods:1.The FTO expression and survival rate in tumors were analyzed.2.FTO in OS cell lines was quantified utilizing western blot and PCR.3.FTO was upregulated and downregulated separately in MG63.4.The impact of FTO on the proliferation and migration of OS cells was evaluated using CCK-8,colony formation,wound healing,and Transwell assays.5.The expression of miR-150-5p in OS cells-derived exosomes was identified.6.The binding of miR-150-5p to FTO was predicted by TargetScan and confirmed by luciferase reporter assay.7.The impact of exosome miR-150-5p on the proliferation and migration of OS cells was investigated.Results:The expression of FTO was higher in OS tissues compared to normal tissues correlating with a worse survival rate.Furthermore,the downregulation of FTO significantly impeded the growth and metastasis of OS cells.Additionally,miR-150-5p,which was downregulated in both OS cells and their derived exosomes,was found to bind to the 3′-UTR of FTO through dual luciferase experiments.Exosomal miR-150-5p was found to decrease the expression of FTO and inhibit cell viability.Conclusions:We identified elevated levels of FTO in OS,which may be attributed to insufficient miR-150-5p levels in both the cells and exosomes.It suggests that the dysregulation of miR-150-5p and its interaction with FTO could potentially promote the development of OS.
基金supported by grants from the National Natural Science Foundation of China(91957124 to J.W.)the National Key Research and Development Program of China(2022YFC2505201 to J.W.).
文摘Dear Editor,Genome-wide association studies(GWAS)revealed a large number of common variants in the human genome associated with an increased risk of diseases.The lead signals of common obesity-associated variants are located within the first intron of the FTO(fat mass and obesity-associated)gene,being the most significant and impactive single-nucleotide polymorphism(SNP)clusters in obesity inheritance[1].Although a strong positive association between these FTO“risk SNPs”(including rs1421085 T>C)and obesity is reported across human populations of diverse ancestry,relatively weak(even none)significant associations have been observed in African populations[2].As known,the frequency of the FTO SNPs varies among different ancestral groups,with the“risk allele”being prevalent in individuals of European ancestry and less common in Asian and African populations.Notably,the linkage disequilibrium(LD)of the“risk SNPs”in African populations was much lower than in non-African populations[3].The reason for the discrepancy remains elusive thus far;however,it could be redefined in the context of the unexpected biological function of the FTO SNPs in vivo[4].
文摘为了探究绵羊FTO(Fat mass and obesity-associated protein)基因的结构和功能,试验采用绵羊皮肤组织RNA-seq获得的CDS序列和生物信息学方法对FTO基因的核苷酸序列的相似性、氨基酸序列、蛋白理化性质、蛋白二、三级结构、亚细胞定位和互作蛋白进行研究。结果表明,绵羊FTO基因CDS区为1518 bp,共编码505个氨基酸,其中亮氨酸(Leu)含量最多(11.1%),组氨酸(His)含量最少(2.6%);FTO蛋白分子式C_(2609)H_(4053)N_(709)O_(771)S_(27),分子的质量为58553.79,理论等电点(pI)为5.28,半衰期为30h,结构不稳定,属于亲水性蛋白,不具有信号肽和跨膜结构域;FTO主要分布在细胞外基质中;多肽链中含有43.17%α螺旋结构、38.61%无规则卷曲、11.49%延伸链和6.73%β折叠结构;FTO与FOXO1、CREB1、ALKBH8、ALKBH5、YTHDF1、YTHDF3、YTHDF2、METTL14、WTAP、METTL310个蛋白可能存在互作。说明绵羊的FTO蛋白主要与RNA甲基化调控相关蛋白互作,为进一步研究其功能提供参考。
文摘为了明确肉质相关基因氟烷基因(Hal)、酸肉基因(RN)和脂肪肥胖相关基因(FTO)在国内外不同猪种群体间的遗传变异特性,本研究以大约克、长白、杜洛克和金华猪等猪种群体为研究对象,应用PCR-RFLP技术分别检测了Hal、RN和FTO基因的多态性,并分析了FTO基因上2个多态位点g.276G>T和c.594C>G的遗传变异情况。结果表明:(1)在杜洛克猪中发现了Hal的基因型Hal NHal n,其频率为0.166,但未发现基因型Hal n Hal n,其它猪种群体中仅检测到了基因型Hal NHal N;(2)在已检测的所有猪种群体中只检测到RN基因的rn/rn基因型,未发现rn/RN和RN/RN基因型;(3)在FTO的g.276G>T位点上,金华猪呈现单态,其它猪种群体均呈现多态。在FTO的c.594C>G位点上,4个猪种群体均呈现多态,3个外来猪种群体均以CC基因型频率较高,而金华猪则以GG基因型频率较高。研究结果提示,由于Hal基因在养猪生产中的利弊双重性,因此在某些猪种群体中仍然存在较高频率的Hal NHal n基因型。此外,结合FTO基因的生理功能和已有的研究结果,可在特定的猪群中将其作为影响猪肉质性状的候选基因。本研究发现FTO的基因型分布在我国优良地方猪种金华猪与国外3个种猪群间存在较大差异,为深入研究不同品种猪的肉质形成机理提供了基础数据。
