BACKGROUND Hepatocellular carcinoma(HCC)is a globally prevalent malignancy associated with high morbidity and mortality.Transfer RNA(tRNA)-derived small RNAs(tsRNAs),a class of small non-coding RNAs originating from t...BACKGROUND Hepatocellular carcinoma(HCC)is a globally prevalent malignancy associated with high morbidity and mortality.Transfer RNA(tRNA)-derived small RNAs(tsRNAs),a class of small non-coding RNAs originating from tRNA,have emerged as potential therapeutic targets in cancers,including HCC.However,the specific tsRNAs involved in HCC and their precise mechanisms remain largely unknown.In this study,we identify and characterize specific tsRNAs involved in the development and progression of HCC,discovering their potential as novel biomarkers for early detection and potential therapeutic targets.AIM To investigate differentially expressed tsRNAs in HCC,identify potential biomarkers,and elucidate the functions and mechanisms of tsRNAs in HCC.METHODS Differentially expressed tsRNAs in Barcelona Clinic Liver Cancer 0/A-stage HCC tissues were identified through high-throughput sequencing.Agarose gel electrophoresis,Sanger sequencing,and quantitative polymerase chain reaction were conducted to detect 5’-tRNA halve(tiRNA)-lysine(Lys)-CTT in tissues and serum samples.The diagnostic performance of 5’-tiRNA-Lys-CTT was evaluated using receiver operating characteristic analysis.HCC cell proliferation was examined using the Cell Counting Kit-8 assay,colony formation assay,and 5-ethynyl-2’-deoxyuridine staining.Additionally,the migratory capability of HCC cells was investigated using Transwell assays.RESULTS The 5’-tiRNA-Lys-CTT demonstrated excellent stability and can be easily detected.Its expression was significantly upregulated in 50 HCC tissues,110 HCC serum samples,and 5 HCC cell lines vs control groups,and the differences were all significant.This elevated expression was strongly associated with clinicopathological characteristics,particularly tumor size,Barcelona Clinic Liver Cancer stage,and cirrhosis of the liver.Receiver operating characteristic analysis revealed superior detection efficiency of 5’-tiRNA-Lys-CTT exhibits for early-stage HCC compared to established markers.Functional assays revealed that 5’-tiRNA-Lys-CTT overexpression promoted cell proliferation and migration,while its inhibition had the opposite effect.Bioinformatics predictions suggest that 5’-tiRNA-Lys-CTT may influence the development and progression of liver cancer by targeting downstream mRNA via metabolic pathways,cancer pathways,and HCC-specific pathways.CONCLUSION The 5’-tiRNA-Lys-CTT levels were higher in early HCC patients.5’-tiRNA-Lys-CTT is a promising diagnostic biomarker for early-stage HCC and may play an oncogenic role in HCC by interacting with downstream mRNA targets via specific pathways.展开更多
Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels.tsRNAs are not on...Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels.tsRNAs are not only degradation fragments but also have biological functions,including those in immune inflammation,metabolic disorders,and cell death.tsRNA dysregulation is closely associated with multiple diseases,including various cancers and acute pancreatitis(AP).AP is a common gastrointestinal disease,and its incidence increases annually.AP development is associated with tsRNAs,which regulate cell injury and induce inflammation,especially pyroptosis and ferroptosis.Notably,serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP.We show the characteristics of tsRNAs and their diagnostic value and function in AP,and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.展开更多
Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in...Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.展开更多
Objective:Bushen Tiansui formula(BSTSF),a traditional Chinese medicine prescription,has been widely used to treat Alzheimer’s disease(AD).However,the mechanisms underlying its effects remain largely unknown.In this s...Objective:Bushen Tiansui formula(BSTSF),a traditional Chinese medicine prescription,has been widely used to treat Alzheimer’s disease(AD).However,the mechanisms underlying its effects remain largely unknown.In this study,a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs(tsRNAs)in the hippocampus,to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs,a novel small non-coding RNA.Methods:To generate a validated AD model,oligomeric amyloid-β_(1-42)(Aβ_(1-42))was injected intracerebroventricularly into rats.The Morris water maze(MWM)test was used to evaluate rat cognitive performance,and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus.Potential targets were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs.Results:The learning and memory deficits of Aβ_(1-42)-induced AD rats,assessed by MWM tests,were clearly ameliorated by BSTSF treatment.A total of 387 tsRNAs were detected in the rat hippocampus.Among them,13 were significantly dysregulated in AD rats compared with sham control rats,while 57 were markedly altered by BSTSF treatment,relative to untreated AD rats(fold change>2 and P<0.05).Moreover,six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR.Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles,via multiple signaling pathways and Gene Ontology biological functions,including cyclic adenosine monophosphate and retrograde endocannabinoid signaling.Conclusion:This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aβ_(1-42)-induced AD rats,demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.展开更多
Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies...Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens upnew possibilities for treatment.展开更多
In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradat...In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.展开更多
The research findings concerning the total synthesis of yeast alanine transfer RNA (yeast alanine tRNA) were successively published in Chinese Science Bulletin (1982) and Science
目的通过分析tsRNA在肺腺癌中的差异表达情况及其表达水平与患者预后的关系,进一步筛选并验证肺腺癌相关tsRNA,以了解其在肺腺癌发生和进展中的相关机制。方法基于计算医学中心数据库筛选出在肺腺癌组织和正常组织中差异表达的tsRNA;基...目的通过分析tsRNA在肺腺癌中的差异表达情况及其表达水平与患者预后的关系,进一步筛选并验证肺腺癌相关tsRNA,以了解其在肺腺癌发生和进展中的相关机制。方法基于计算医学中心数据库筛选出在肺腺癌组织和正常组织中差异表达的tsRNA;基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析tsRNA表达水平对肺腺癌患者预后的影响;基于TRFtarget2.0和tRFTar数据库预测靶基因;基于DAVID、KOBA KEGG在线网站进行基因本体论(Gene Ontology,GO)富集分析和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析;基于阿拉巴马大学伯明翰分校癌症数据分析门户(the University of Alabama at Birmingham CANcer data analysis Portal,UALCAN)分析靶基因在肺腺癌组织和正常组织中的表达水平。采用增殖实验、迁移实验、侵袭实验验证tRF-19-69M8LOJX在肺腺癌细胞中的生物学功能。结果与正常组织相比,tRF-19-69M8LOJX在肺腺癌组织中表达上调(log2FC=4.28,FDR<0.05)。高表达水平的tRF-19-69M8LOJX预示着更短的无进展生存期(HR=1.565,95%CI=1.142~2.145,P=0.005);过表达tRF-19-69M8LOJX促进A549细胞的增殖、迁移(P<0.001)和侵袭(P=0.009);COL1A1(P=0.002)和VCAN(P=0.022)在tRF-19-69M8LOJX过表达细胞模型中显著上调。结论tRF-19-69M8LOJX在肺腺癌组织的表达水平上调,与患者不良预后密切相关,可能在肺腺癌的发生发展中起着重要作用。展开更多
转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传...转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传调控因子方式,在多种生物体的生理和病理过程中发挥重要作用,因此,其逐渐成为生物医学的研究热点而引起广泛关注。而且越来越多的证据显示,tsRNA通过对应激反应、细胞增殖与凋亡、神经发育、突触可塑性、神经炎症与免疫调节、表观遗传、RNA加工和蛋白质翻译调控等参与许多神经精神疾病的发生和发展过程。该文主要就tsRNA的生成和分类及其生物学功能,阐述tsRNA在神经发育和神经精神疾病中的作用和可能作用机制,从而进一步揭示tsRNA作为神经精神疾病可靠生物标志物和治疗靶点的潜力。展开更多
目的:鉴定人肝母细胞瘤HepG2细胞中响应DNA损伤的转运RNA衍生的小RNA(transfer RNAderived small RNA,tsRNA)的表达特征,并研究其潜在功能。方法:本研究基于配对的HepG2细胞和敲除TP53基因的HepG2细胞,采用阿霉素(adriamycin,ADR)成功构...目的:鉴定人肝母细胞瘤HepG2细胞中响应DNA损伤的转运RNA衍生的小RNA(transfer RNAderived small RNA,tsRNA)的表达特征,并研究其潜在功能。方法:本研究基于配对的HepG2细胞和敲除TP53基因的HepG2细胞,采用阿霉素(adriamycin,ADR)成功构建DNA损伤的细胞模型,并进行小非编码RNA的转录组分析,系统地鉴定一批响应ADR并参与p53调节的tsRNA,利用京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)进行了功能富集分析。此外,经沉默目标tsRNA基因表达后,通过CCK-8实验和平板集落形成实验初步证实了目标tsRNA在HepG2细胞模型中的生物学功能。结果:DNA损伤可诱导一批参与p53调节的tsRNA,其中tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)和tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)在HepG2细胞中的表达上调最为显著(P<0.05)。沉默tRF-5-1或tRF-i-1基因可抑制HepG2细胞的增殖活力(P<0.05)。结论:HepG2细胞模型中可以鉴定一组响应DNA损伤的tsRNA,且tsRNA可以促进HepG2细胞的增殖活力,提示tsRNA在肝脏细胞的恶性增殖中可能扮演重要角色。展开更多
外泌体作为由肿瘤细胞等多种细胞分泌的双层脂质囊泡,富含转运RNA(transfer RNA,tRNA)衍生的小分子RNA(tRNA-derived small RNA,tsRNA)等生物活性分子,在细胞通讯中发挥重要作用。tsRNAs源自前体tRNA或成熟tRNA,其表达水平在肿瘤患者的...外泌体作为由肿瘤细胞等多种细胞分泌的双层脂质囊泡,富含转运RNA(transfer RNA,tRNA)衍生的小分子RNA(tRNA-derived small RNA,tsRNA)等生物活性分子,在细胞通讯中发挥重要作用。tsRNAs源自前体tRNA或成熟tRNA,其表达水平在肿瘤患者的体液中存在显著差异。外泌体来源的tsRNA在肿瘤患者的血浆、唾液等体液中大量存在。最新研究表明,其参与调控肿瘤细胞增殖、侵袭、迁移及耐药。此外,因其稳定性和组织特异性,tsRNAs在液体活检中作为肿瘤临床生物标志物展现出巨大潜力。本文全面总结了外泌体来源tsRNA在肿瘤中的生物学功能及其作为肿瘤诊疗生物标志物的广阔应用前景。展开更多
基金Supported by the Scientific Research Project of Nantong Municipal Commission of Health and Family Planning,No.QN2023001.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is a globally prevalent malignancy associated with high morbidity and mortality.Transfer RNA(tRNA)-derived small RNAs(tsRNAs),a class of small non-coding RNAs originating from tRNA,have emerged as potential therapeutic targets in cancers,including HCC.However,the specific tsRNAs involved in HCC and their precise mechanisms remain largely unknown.In this study,we identify and characterize specific tsRNAs involved in the development and progression of HCC,discovering their potential as novel biomarkers for early detection and potential therapeutic targets.AIM To investigate differentially expressed tsRNAs in HCC,identify potential biomarkers,and elucidate the functions and mechanisms of tsRNAs in HCC.METHODS Differentially expressed tsRNAs in Barcelona Clinic Liver Cancer 0/A-stage HCC tissues were identified through high-throughput sequencing.Agarose gel electrophoresis,Sanger sequencing,and quantitative polymerase chain reaction were conducted to detect 5’-tRNA halve(tiRNA)-lysine(Lys)-CTT in tissues and serum samples.The diagnostic performance of 5’-tiRNA-Lys-CTT was evaluated using receiver operating characteristic analysis.HCC cell proliferation was examined using the Cell Counting Kit-8 assay,colony formation assay,and 5-ethynyl-2’-deoxyuridine staining.Additionally,the migratory capability of HCC cells was investigated using Transwell assays.RESULTS The 5’-tiRNA-Lys-CTT demonstrated excellent stability and can be easily detected.Its expression was significantly upregulated in 50 HCC tissues,110 HCC serum samples,and 5 HCC cell lines vs control groups,and the differences were all significant.This elevated expression was strongly associated with clinicopathological characteristics,particularly tumor size,Barcelona Clinic Liver Cancer stage,and cirrhosis of the liver.Receiver operating characteristic analysis revealed superior detection efficiency of 5’-tiRNA-Lys-CTT exhibits for early-stage HCC compared to established markers.Functional assays revealed that 5’-tiRNA-Lys-CTT overexpression promoted cell proliferation and migration,while its inhibition had the opposite effect.Bioinformatics predictions suggest that 5’-tiRNA-Lys-CTT may influence the development and progression of liver cancer by targeting downstream mRNA via metabolic pathways,cancer pathways,and HCC-specific pathways.CONCLUSION The 5’-tiRNA-Lys-CTT levels were higher in early HCC patients.5’-tiRNA-Lys-CTT is a promising diagnostic biomarker for early-stage HCC and may play an oncogenic role in HCC by interacting with downstream mRNA targets via specific pathways.
基金Supported by the Central South University Innovation-Driven Research Programme,No.2023CXQD075。
文摘Transfer RNA(tRNA)-derived fragments,a new type of tRNA-derived small RNA(tsRNA),can be cleaved from tRNA by enzymes to regulate target gene expression at the transcriptional and translational levels.tsRNAs are not only degradation fragments but also have biological functions,including those in immune inflammation,metabolic disorders,and cell death.tsRNA dysregulation is closely associated with multiple diseases,including various cancers and acute pancreatitis(AP).AP is a common gastrointestinal disease,and its incidence increases annually.AP development is associated with tsRNAs,which regulate cell injury and induce inflammation,especially pyroptosis and ferroptosis.Notably,serum tRF36 has the potential to serve as a non-invasive diagnostic biomarker and leads to pancreatic acinar cell ferroptosis causing inflammation to promote AP.We show the characteristics of tsRNAs and their diagnostic value and function in AP,and discuss the potential opportunities and challenges of using tsRNAs in clinical applications and research.
基金supported by grants from the National Natural Science Foundation of China,Nos.81471238,81771327Construction of Central Nervous System Injury Basic Science and Clinical Translational Research Platform,Budget of Beijing Municipal Health Commission 2020,No.PXM2020_026280_000002(all to BYL)。
文摘Transfer RNA(t RNA)-derived small RNAs(ts RNAs) are a recently established family of regulatory small non-coding RNAs that modulate diverse biological processes. Growing evidence indicates that ts RNAs are involved in neurological disorders and play a role in the pathogenesis of neurodegenerative disease. However, whether ts RNAs are involved in traumatic brain injury-induced secondary injury remains poorly understood. In this study, a mouse controlled cortical impact model of traumatic brain injury was established, and integrated ts RNA and messenger RNA(m RNA) transcriptome sequencing were used. The results revealed that 103 ts RNAs were differentially expressed in the mouse model of traumatic brain injury at 72 hours, of which 56 ts RNAs were upregulated and 47 ts RNAs were downregulated. Based on micro RNA-like seed matching and Pearson correlation analysis, 57 differentially expressed ts RNA-m RNA interaction pairs were identified, including 29 ts RNAs and 26 m RNAs. Moreover, Gene Ontology annotation of target genes revealed that the significantly enriched terms were primarily associated with inflammation and synaptic function. Collectively, our findings suggest that ts RNAs may be associated with traumatic brain injury-induced secondary brain injury, and are thus a potential therapeutic target for traumatic brain injury. The study was approved by the Beijing Neurosurgical Institute Animal Care and Use Committee(approval No. 20190411) on April 11, 2019.
基金supported by the National Natural Science Foundation of China(No.81603670,81873169)the Hunan Provincial Natural Science Foundation of China(No.2017JJ3459,2020JJ4803)。
文摘Objective:Bushen Tiansui formula(BSTSF),a traditional Chinese medicine prescription,has been widely used to treat Alzheimer’s disease(AD).However,the mechanisms underlying its effects remain largely unknown.In this study,a rat AD model was used to study the effects of BSTSF on cognitive performance and expression of transfer RNA-derived small RNAs(tsRNAs)in the hippocampus,to determine whether treatment of AD with BSTSF could regulate the expression of tsRNAs,a novel small non-coding RNA.Methods:To generate a validated AD model,oligomeric amyloid-β_(1-42)(Aβ_(1-42))was injected intracerebroventricularly into rats.The Morris water maze(MWM)test was used to evaluate rat cognitive performance,and tsRNA-sequencing was conducted to examine tsRNA expression in the rat hippocampus.Potential targets were validated by quantitative real-time polymerase chain reaction(qRT-PCR).Bioinformatic analyses were conducted to investigate the biological function of candidate tsRNAs.Results:The learning and memory deficits of Aβ_(1-42)-induced AD rats,assessed by MWM tests,were clearly ameliorated by BSTSF treatment.A total of 387 tsRNAs were detected in the rat hippocampus.Among them,13 were significantly dysregulated in AD rats compared with sham control rats,while 57 were markedly altered by BSTSF treatment,relative to untreated AD rats(fold change>2 and P<0.05).Moreover,six BSTSF treatment-related tsRNAs were identified and validated by qRT-PCR.Bioinformatic analyses indicated that the six treatment-related tsRNAs had potential therapeutic roles,via multiple signaling pathways and Gene Ontology biological functions,including cyclic adenosine monophosphate and retrograde endocannabinoid signaling.Conclusion:This study identified a previously uncharacterized mechanism underlying the effects of BSTSF in alleviating the learning and memory deficits in Aβ_(1-42)-induced AD rats,demonstrating that tsRNAs are potential therapeutic targets of BSTSF in the treatment of AD.
基金was supported by the National Natural Science Foundation of China(Nos.82272411 and 82072363)the Jiangsu Provincial Medical Key Discipline(Laboratory)(No.ZDXK202240)the Science and Technology Project of Jiangsu Province(No.BE2023741),China。
文摘Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens upnew possibilities for treatment.
文摘In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.
文摘The research findings concerning the total synthesis of yeast alanine transfer RNA (yeast alanine tRNA) were successively published in Chinese Science Bulletin (1982) and Science
文摘目的通过分析tsRNA在肺腺癌中的差异表达情况及其表达水平与患者预后的关系,进一步筛选并验证肺腺癌相关tsRNA,以了解其在肺腺癌发生和进展中的相关机制。方法基于计算医学中心数据库筛选出在肺腺癌组织和正常组织中差异表达的tsRNA;基于癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析tsRNA表达水平对肺腺癌患者预后的影响;基于TRFtarget2.0和tRFTar数据库预测靶基因;基于DAVID、KOBA KEGG在线网站进行基因本体论(Gene Ontology,GO)富集分析和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路分析;基于阿拉巴马大学伯明翰分校癌症数据分析门户(the University of Alabama at Birmingham CANcer data analysis Portal,UALCAN)分析靶基因在肺腺癌组织和正常组织中的表达水平。采用增殖实验、迁移实验、侵袭实验验证tRF-19-69M8LOJX在肺腺癌细胞中的生物学功能。结果与正常组织相比,tRF-19-69M8LOJX在肺腺癌组织中表达上调(log2FC=4.28,FDR<0.05)。高表达水平的tRF-19-69M8LOJX预示着更短的无进展生存期(HR=1.565,95%CI=1.142~2.145,P=0.005);过表达tRF-19-69M8LOJX促进A549细胞的增殖、迁移(P<0.001)和侵袭(P=0.009);COL1A1(P=0.002)和VCAN(P=0.022)在tRF-19-69M8LOJX过表达细胞模型中显著上调。结论tRF-19-69M8LOJX在肺腺癌组织的表达水平上调,与患者不良预后密切相关,可能在肺腺癌的发生发展中起着重要作用。
文摘转运核糖核酸(tRNA)衍生的小分子RNA(transfer-RNA derived small RNA,tsRNA)是近年来新发现的一类由成熟tRNA或其前体通过特殊的内切酶介导产生的非编码RNA。已有的研究揭示,tsRNA能够在转录及转录后水平上调控基因表达,能以表观遗传调控因子方式,在多种生物体的生理和病理过程中发挥重要作用,因此,其逐渐成为生物医学的研究热点而引起广泛关注。而且越来越多的证据显示,tsRNA通过对应激反应、细胞增殖与凋亡、神经发育、突触可塑性、神经炎症与免疫调节、表观遗传、RNA加工和蛋白质翻译调控等参与许多神经精神疾病的发生和发展过程。该文主要就tsRNA的生成和分类及其生物学功能,阐述tsRNA在神经发育和神经精神疾病中的作用和可能作用机制,从而进一步揭示tsRNA作为神经精神疾病可靠生物标志物和治疗靶点的潜力。
文摘目的:鉴定人肝母细胞瘤HepG2细胞中响应DNA损伤的转运RNA衍生的小RNA(transfer RNAderived small RNA,tsRNA)的表达特征,并研究其潜在功能。方法:本研究基于配对的HepG2细胞和敲除TP53基因的HepG2细胞,采用阿霉素(adriamycin,ADR)成功构建DNA损伤的细胞模型,并进行小非编码RNA的转录组分析,系统地鉴定一批响应ADR并参与p53调节的tsRNA,利用京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)进行了功能富集分析。此外,经沉默目标tsRNA基因表达后,通过CCK-8实验和平板集落形成实验初步证实了目标tsRNA在HepG2细胞模型中的生物学功能。结果:DNA损伤可诱导一批参与p53调节的tsRNA,其中tRF-5-1(tRF-5_tRNA-Gly-TCC-2-1)和tRF-i-1(tRF i_tRNA-Tyr-GTA-11-1)在HepG2细胞中的表达上调最为显著(P<0.05)。沉默tRF-5-1或tRF-i-1基因可抑制HepG2细胞的增殖活力(P<0.05)。结论:HepG2细胞模型中可以鉴定一组响应DNA损伤的tsRNA,且tsRNA可以促进HepG2细胞的增殖活力,提示tsRNA在肝脏细胞的恶性增殖中可能扮演重要角色。
文摘外泌体作为由肿瘤细胞等多种细胞分泌的双层脂质囊泡,富含转运RNA(transfer RNA,tRNA)衍生的小分子RNA(tRNA-derived small RNA,tsRNA)等生物活性分子,在细胞通讯中发挥重要作用。tsRNAs源自前体tRNA或成熟tRNA,其表达水平在肿瘤患者的体液中存在显著差异。外泌体来源的tsRNA在肿瘤患者的血浆、唾液等体液中大量存在。最新研究表明,其参与调控肿瘤细胞增殖、侵袭、迁移及耐药。此外,因其稳定性和组织特异性,tsRNAs在液体活检中作为肿瘤临床生物标志物展现出巨大潜力。本文全面总结了外泌体来源tsRNA在肿瘤中的生物学功能及其作为肿瘤诊疗生物标志物的广阔应用前景。
