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15-Methylcytosine RNA Methylation in Arabidopsis Thaliana显示文摘5-Methylcytosine (m 5 C ) 是描绘得好的 DNA 修正,并且主要也在初核质和优核质在丰富的非编码的 RNA 被报导。然而,分发和 m 5 在植物 mRNAs 的 C 仍然保持大部分未知。这里,我们报导 RNA m 5 在由使用 m 5 C RNA immunoprecipitation 由一条深定序的途径列在后面(m 5 C-RIP-seq ) 。LC-MS/MS 和点污点分析揭示 m 5 在各种各样的纸巾并且在不同发展阶段的 C mRNA 修正。m 5 C-RIP-seq 分析识别了 6045 m 5 在 4465 的 C 山峰在年轻幼苗表示了基因。我们发现那 m 5 C 在编码序列,二座山峰在开始 codons 以后并且在站 codons 前立即定位了被充实,并且随低翻译与 mRNAs 被联系活动。我们进一步表明了那 RNA (cytosine-5 )-methyltransferase,tRNA 特定的 methyltransferase 4B (TRM4B ) ,展览 m 5 C RNA methyltransferase 活动。在 TRM4B 的变化在根开发和减少的 m 5 C 山峰。TRM4B 影响涉及根开发的基因的抄本层次,它断然与他们的 mRNA 稳定性和 m 5 C 层次。我们的结果建议那 m 5 在 mRNA 的 C 是新 epitranscriptome 标记 inArabidopsis,并且这修正的那条规定是基因的不可分的部分规章的网络位于 \O 下面植物开发。Xuean Cui Zhe Liang Lisha Shen Qian Zhang Shengjie Bao Yuke Geng Bin Zhang Vonny Leo Leah A. Vardy Tiegang Lu Xiaofeng Gu Hao Yu 2017Molecular Plant2017,10,11:19
2Effects and mechanisms of Bazhen decoction,Siwu decoction,and Sijunzi decoction on 5-fluorouracil-induced anemia in mice显示文摘OBJECTIVE:To investigate the effects of Bazhen decoction(BZD),Siwu decoction(SWD) and Sijunzi decoction(SJZD) in mice with anemia induced by5-fluorouracil(5-FU) and discussed the possible pharmacological hematopoietic mechanism to provide experimental evidence for the clinical use of the three classical prescriptions in the treatment of anemia.METHODS:Anemia was induced by intravenous injection of 5-FU and 80 female Kunming mice were randomly,assigned to oral administration of SWD,SJZD,or BZD daily for 10 days.Peripheral blood cells count and bone marrow cell cycle were monitored to evaluate anti-anemia effects.Serum cytokines,interferon-γ(IFN-γ),interleukin-3(IL-3),erythropoietin(EPO),granulocyte-macrophage colonystimulating factor(GM-CSF),and tumor necrosis factor-α(TNF-α) were assayed.EPO m RNA expression was assayed in kidney and liver tissue homogenates.RESULTS:BZD and SWD significantly increased the number of red blood cells,hemoglobin concentration,and hematocrit,promoted bone marrow cells to enter the cell cycle,proliferate and differentiate,significantly increased IL-3 secretion,and significantly inhibited IFN-γ secretion.BZD stimulated transcription of EPO m RNA in the kidney and liver and enhanced serum EPO expression.A therapeutic effect of SJZD was not observed.CONCLUSION:BZD and SWD treatment specifically enhanced hematopoietic function and mediated myelopoiesis by altering serum cytokines levels and accelerating entry of bone marrow cells into the cell cycle.Better curative effects were achieved via nourishing both Qi and blood(BZD) than by enriching the blood(SWD) or invigorating Qi(SWZD)alone.Tian Yunan Xiang Yuke Wan Guoran Wan Dong Zhu Huifeng Wang Tao Yang Xian 2016Journal of Traditional Chinese Medicine2016,36,4:12
3Internet of Things to network smart devices for ecosystem monitoring显示文摘Smart, real-time, low-cost, and distributed ecosystem monitoring is essential for understanding and managing rapidly changing ecosystems. However, new techniques in the big data era have rarely been introduced into operational ecosystem monitoring, particularly for fragile ecosystems in remote areas.We introduce the Internet of Things(IoT) techniques to establish a prototype ecosystem monitoring system by developing innovative smart devices and using IoT technologies for ecosystem monitoring in isolated environments. The developed smart devices include four categories: large-scale and nonintrusive instruments to measure evapotranspiration and soil moisture, in situ observing systems for CO2 and d13 C associated with soil respiration, portable and distributed devices for monitoring vegetation variables, and Bi-CMOS cameras and pressure trigger sensors for terrestrial vertebrate monitoring. These new devices outperform conventional devices and are connected to each other via wireless communication networks. The breakthroughs in the ecosystem monitoring IoT include new data loggers and longdistance wireless sensor network technology that supports the rapid transmission of data from devices to wireless networks. The applicability of this ecosystem monitoring IoT is verified in three fragile ecosystems, including a karst rocky desertification area, the National Park for Amur Tigers, and the oasis-desert ecotone in China. By integrating these devices and technologies with an ecosystem monitoring information system, a seamless data acquisition, transmission, processing, and application IoT is created. The establishment of this ecosystem monitoring IoT will serve as a new paradigm for ecosystem monitoring and therefore provide a platform for ecosystem management and decision making in the era of big data.Xin Li Ning Zhao Rui Jin Shaomin Liu Xiaomin Sun Xuefa Wen Dongxiu Wu Yan Zhou Jianwen Guo Shiping Chen Ziwei Xu Mingguo Ma Tianming Wang Yonghua Qu Xinwei Wang Fangming Wu Yuke Zhou 2019Science Bulletin2019,64,17:10
4An H3K27me3 demethylase-HSFA2 regulatory loop orchestrates transgenerational thermomemory in Arabidopsis显示文摘Global warming has profound effects on plant growth and fitness.Plants have evolved sophisticated epigenetic machinery to respond quickly to heat,and exhibit transgenerational memory of the heat-induced release of post-transtriptional gene silencing(PTGS).However,how thermomemory is transmitted to progeny and the physiological relevance are elusive.Here we show that heat-induced HEAT SHOCK TRANSCRIPTION FACTOR A2(HSFA2)directly activates the H3K27me3 demethylase RELATIVE OF EARLY FLOWERING 6(REF6),which in turn derepresses HSFA2.REF6 and HSFA2 establish a heritable feedback loop,and activate an E3 ubiquitin ligase,SUPPRESSOR OF GENE SILENCING 3(SGS3)-INTERACTING PROTEIN 1(SGIP1).SGIP1-mediated SGS3 degradation leads to inhibited biosynthesis of trans-acting siRNA(tasiRNA).The REF&HSFA2 loop and reduced tasiRNA converge to release HEAT-INDUCED TAS1 TARGET 5(HTT5),which drives early flowering but attenuates immunity.Thus,heat induces transmitted phe no types via a coordi nated epigenetic network involvi ng histone demethylases,tran scriptio n factors,and tasiRNAs,ensuring reproductive success and transgenerational stress adaptation.Junzhong Liu Lili Feng Xueting Gu Xian Deng Qi Qiu Qun Li Yingying Zhang Muyang Wang Yiwen Deng Ertao Wang Yuke He Isabel Baurle Jianming Li Xiaofeng Cao Zuhua He 2019Cell Research2019,29,5:10
5NK cell education via nonclassical MHC and non-MHC ligands显示文摘生来的杀手(NK ) 房间教育,为完成功能的成熟和自我忍耐的一个过程,被在自我专业 histocompatibility 建筑群一级(MHC-I ) 之间的相互作用以前定义分子和他们的特定的禁止的受体。在过去的几年,种证据在 NK 房间教育加亮 nonclassical MHC-I 和 non-MHC-I 分子的重要角色。此处,我们考察 NK 房间教育的当前的知识,与 nonclassical MHC-I- 和 non-MHC-I-dependent 教育的一个特别焦点,并且把他们与古典 MHC-I-dependent 教育理论作比较。另外,我们更新并且由介绍限制模型扩大这个理论,重估数量和质量控制,并且阐明,讨论 cis 和 trans 特征在肿瘤和病毒感染的 NK 房间教育的冗余性。Yuke He Zhigang Tian 2017Cellular & Molecular Immunology2017,14,4:9
6A modified high-efficiency thermal asymmetric interlaced PCR method for amplifying long unknown flanking sequences显示文摘Rapid and efficient isolation of unknown flanking DNA sequences adjacent to known regions is important for molecular biology research.For this purpose,several PCR-based methods have been reported,including inverse PCR(Uchiyama and Watanabe,2006),ligation-mediated PCR(Yan et al.,2003;Ballester et al.,2005;Wang et al.,2007;Trinh et al.,2012)and randomly primed PCR(Liu and Whittier,1995;Liu et al.,1995;Antal et al.Jiantao Tan Qi Gong Suize Yu Yuke Hou Dongchang Zeng Qinlong Zhu Yao-Guang Liu 2019Journal of Genetics and Genomics2019,46,7:7
7基层医疗国际分类对城市全科医疗门诊老年患者就诊原因及服务需求的评价显示文摘目的 了解北京和天津城市全科医疗诊所中老年患者的患病情况和就诊原因 ;探索以基层医疗国际分类 (ICPC)方法客观评价居民医疗服务需求的状况。方法 采用典型抽样的方法 ,选取在 1999年 11月~ 2 0 0 0年 2月间、每个月前 2周中因不同原因到上述全科医疗门诊就诊的≥ 6 5岁的老人作为研究对象 ,共获得样本量为 2 85 9人次 ;由全科医生对其就诊情况进行记录 ,并使用基层医疗国际分类 (ICPC - 2 )对所记录的就诊原因和健康问题进行分类和编码。进而将分析结果与香港的研究结果进行比较。结果 老年人的首位就诊原因是头晕 ;就诊原因中的 4 1 6 %和健康问题 (诊断 )中的 6 0 3%属于心血管系统 ;2 4 6 %的患者患有高血压和相关疾病 ;研究地区与香港地区老年人的健康问题有所不同。结论 ICPC是研究居民就诊原因和医疗服务需求的有效而实用的工具。研究地区中老年人的主要健康问题是慢性疾患 ,特别是心血管疾病 ,此提示慢性病是目前及今后全科医疗服务的主要内容 ,而全科医生的继续教育亦应顺应患者的需求。路孝琴 贾庆春 梁万年 Wun Yuke Tsan 瓮学清 2004中国全科医学2004,7,12:7
8Characteristics of microbial community involved in early biofilms formation under the influence of wastewater treatment plant effluent显示文摘Effluents from wastewater treatment plants(WWTPs) containing microorganisms and residual nutrients can influence the biofilm formation. Although the process and mechanism of bacterial biofilm formation have been well characterized, little is known about the characteristics and interaction of bacteria, archaea and eukaryotes in the early colonization, especially under the influence of WWTP effluent. The aim of this study was to characterize the important bacterial, archaeal and eukaryotic species in the early stage of biofilm formation downstream of the WWTP outlet. Water and biofilm samples were collected 24 and 48 hr after the deposition of bio-cords in the stream. Illumina Miseq sequencing of the 16 S and 18 S rDNA showed that, among the three domains, the bacterial biofilm community had the largest alpha and beta diversity. The early bacterial colonizers appeared to be 'biofilm-specific', with only a few dominant operational taxonomic units(OTUs) shared between the biofilm and the ambient water environment. Alpha-proteobacteria and Ciliophora tended to dominate the bacterial and eukaryotic communities, respectively, of the early biofilm already at 24 hr, whereas archaea played only a minor role during the early stage of colonization. The network analysis showed that the three domains of microbial community connected highly during the early colonization and it might be a characteristic of the microbial communities in the biofilm formation process where co-occurrence relationships could drive coexistence and diversity maintenance within the microbial communities.Yuke Peng Jie Li Junling Lu Lin Xiao Liuyan Yang 2018Journal of Environmental Sciences2018,30,4:6
9Sequence modification of merB gene and high organomercurial resistance of transgenic tobacco plants显示文摘Mercury pollution has caused severe damage to environment and great attention has been paid to its control. Phytoremediation may become one of the most efficient measures to recover the polluted soil since it is economical, highly efficient and friendly to environment. In this report, plant genetic engineering methods were employed to modify the DNA sequence of merB genes that catalyze the conversion of organomercurals into ionic mercury. The modified mer-Bhe genes were introduced into tobacco by Agrobacterium, and the resultant transgenic plants were verified by Southern and Northern hybridization. High level of organomercu-rial resistance was detected on progenies of transgenic plants, some of which were resistant to PMA (phenyl mercury acetate) of 2.5μmol/L whereas 0.1μmol/L PMA killed the seedlings of wild-type tobacco in soiless culrure. With the increase of PMA concentration, the inhibition of the seedling growth became apparent. This result makes it possible to breed mercury-resistant tobaccoTIAN Jilin SHEN Ruijuan HE Yuke 2002Chinese Science Bulletin2002,47,24:6
10WSe2 2D p-type semiconductor-based electronic devices for information technology:Design,preparation,and applications显示文摘The pioneering exfoliation of monolayer tungsten diselenide has greatly inspired researchers toward semiconducting applications.WSe2 belongs to a family of transition-metal dichalcogenides.Similar to graphene,WSe2 and analogous dichalcogenides have layered structures with weak van der Waals interactions between two adjacent layers.First,the readers are presented with the fundamentals of WSe2,such as types,morphologies,and properties.Here,we report the characterization principles and practices such as microscopy,spectroscopy,and diffraction.Second,the methods for obtaining high-quality WSe2,such as exfoliation,hydrothermal and chemical vapor deposition,are briefly listed.With advantages of light weight,flexibility,and high quantum efficiency,2D materials may have a niche in optoelectronics as building blocks in p-n junctions.Therefore,we introduce a state-of-the-art demonstration of heterostructure devices employing the p-type WSe2 semiconductor.The device architectures include field-effect transistors,photodetectors,gas sensors,and photovoltaic solar cells.Due to its unique electronic,optical,and energy band properties,WSe2 has been increasingly investigated due to the conductivity of the p-type charge carrier upon palladium contact.Eventually,the dynamic research on WSe2 and van der Waals heterostructures is summarized to arouse the passion of the 2D research community.Qilin Cheng Jinbo Pang Dehui Sun Jingang Wang Shu Zhang Fan Liu Yuke Chen Ruiqi Yang Na Liang Xiheng Lu Yanchen Ji Jian Wang Congcong Zhang Yuanhua Sang Hong Liu Weijia Zhou 2020InfoMat2020,2,4:5
11New Insights into the Late Triassic Nadigangri Formation of Northern Qiangtang, Tibet, China: Constraints from U-Pb Ages and Hf Isotopes of Detrital and Magmatic Zircons显示文摘We report here U-Pb age and in situ Hf isotopic results for detrital and magmatic zircons from one conglomerate and four tuffite samples from the Late Triassic Nadigangri Formation across the North Qiangtang depression, Tibet. Coupled with previously published data in the region, this paper proposes new insights into the geochronological framework for the Nadigangri Formation. The deposition ages of tuffite from top to bottom in the Woruo Mountain, Quem Co and Dongqu River, are 203 Ma, 226 Ma, 221.5 Ma and 221.1 Ma, respectively. The detrital zircons yield a younger cluster of ages of 201.5–225 Ma from the conglomerate of the Quem Co Formation. The Late Triassic Nadigangri Formation defines a temporal range approximately between 201 and 225 Ma(Norian-Rhaetian), including three predominant groups of 220–225 Ma, 210–217 Ma and 201–205 Ma, which correspond with the three main rifting episodes of initial rifting, further rifting and final rifting. Positive εHf(t) value and low model ages in younger detrital zircons suggests a juvenile character. However, the Hf isotopes of magmatic zircons display the presence of reworked ancient crust with 1.1–1.8 Ga. These results provide strong constraints not only on the temporal range of the Late Triassic Nadigangri Formation, but also on the onset of the Qiangtang Mesozoic rift basin.LI Xueren WANG Jian CHENG Leli FU Xiugen WANG Yuke 2018Acta Geologica Sinica(English Edition)2018,92,4:5
12城市社区卫生服务站老年患者就诊原因及患病状况研究显示文摘路孝琴 贾庆春 梁万年 Wun Yuke Tsan 彭晓霞 2004中华全科医师杂志2004,3,5:5
13Clinicopathological and prognostic role of MMP-9 in esophageal squamous cell carcinoma: a meta-analysis显示文摘Objective:Many studies reported that matrix metalloproteinase-9(MMP-9)participated in the development of esophageal squamous cell carcinoma(ESCC)and resulted in poor prognosis,however,they all included few patients and had inconsistent results.So we conducted a meta-analysis to explore the correlation between overexpression of MMP-9 and the clinicopathological characteristics and overall survival(OS)of ESCC.Methods:PubMed,EMBASE,Web of Science,Chinese Biomedical Literature Database,Google Scholar and other databases were searched for relevant studies.The Newcastle-Ottawa quality assessment scale was used to assess the methodological quality of included study and RevMan 5.2 software was used to conduct meta-analysis.Results:A total of 35 studies were included,and the results of meta-analysis showed that overexpression of MMP-9 was associated with grade of differentiation[well/moderate vs.poor:odds ratio(OR):0.39,95%confidence interval(CI):0.29-0.52;P<0.00001],lymph node metastasis(negative vs.positive:OR:0.24,95%CI:0.16-0.34;P<0.00001),TNM stage(T1/T2 vs.T3/T4:OR:0.28,95%CI:0.14-0.54;P=0.0002),the depth of invasion(T1/T2 vs.T3/T4:OR:0.29,95%CI:0.17-0.49;P<0.00001),and vascular invasion of ESCC(negative vs.positive:OR:0.35,95%CI:0.21-0.58;P<0.0001),and also associated with poor overall survival of ESCC(HR:2.17,95%CI:1.32-3.57;P=0.002).Subgroup analysis showed that more than 10%of carcinoma cell staining was associated with significant increase of mortality risk(HR:2.44,95%CI:1.16-5.15;P=0.02),and sensitive analysis suggested that MMP-9 was an independent prognostic factor in ESCC(HR:1.49,95%CI:1.16-1.91;P=0.002).Conclusions:On the basis of limited evidence,overexpression of MMP-9 may be a potential independent prognosis factor of ESCC patients in Asia,and high-quality studies assessing the prognostic significance of MMP-9 for ESCC patients are still needed.Rong Zeng Lei Duan Yuke Kong Yaojun Liang Xiaolu Wu Xuequan Wei Kehu Yang 2013Chinese Journal of Cancer Research2013,25,6:5
14Adenine Methylation: New Epigenetic Marker ol DNA and mRNA显示文摘Zhe Liang Yuke Geng Xiaofeng GU 2018Molecular Plant2018,11,10:4
15Modeling unsaturated flow in fractured rocks with scaling relationships between hydraulic parameters显示文摘Modeling unsaturated flow in fractured rocks is essential in various subsurface engineering applications,but it remains a great challenge due to the difficulties in determining the unsaturated hydraulic properties of rocks that contain various scales of fractures.It is generally accepted that the van Genuchten(VG)model can be applied to fractured rocks,provided that the hydraulic parameters could be representatively determined.In this study,scaling relationships between the VG parameters(a and n)and hydraulic conductivity(K)across 8 orders of magnitude,from 10^(-10)m/s to 10^(-2)m/s,were proposed by statistical analysis of data obtained from 1416 soil samples.The correlations were then generalized to predict the upper bounds of VG parameters for fractured rocks from the K data that could be obtained more easily under field conditions,and were validated against a limited set of data from cores,fractures and fractured rocks available in the literature.The upper bound estimates significantly narrow the ranges of VG parameters,and the representative values of a and n for fractured rocks at the field scale can then be determined with confidence by inverse modeling using groundwater observations in saturated zones.The proposed methodology was applied to saturated-unsaturated flow modeling in the right-bank slope at the Baihetan dam site with a continuum approach,showing that most of the flow behaviors in fractured rocks in this complex hydrogeological condition could be properly reproduced.The proposed method overcomes difficulties in suction measurement in fractured rocks with strong heterogeneity,and provides a feasible way for modeling of saturated-unsaturated flow in fractured rocks with acceptable engineering accuracy.Yi-Feng Chen Yuke Ye Ran Hu Zhibing Yang Chuang-Bing Zhou 2022Journal of Rock Mechanics and Geotechnical Engineering2022,14,6:4
16Effects of Neo-Tethyan evolution on the petroleum system of Persian Gulf Superbasin显示文摘Considering the Neo-Tethyan tectonic process and the resulting environmental changes,a geodynamic model of“one-way train loading”is proposed to analyze the formation and evolution mechanism of the Persian Gulf Superbasin with the most abundant hydrocarbons in the world.The Persian Gulf Superbasin has long been in a passive continental margin setting since the Late Paleozoic in the process of unidirectional subduction,forming a superior regional space of hydrocarbon accu-mulation.During the Jurassic-Cretaceous,the Persian Gulf Superbasin drifted slowly at low latitudes,and developed multiple superimposed source-reservoir-caprock assemblages as a combined result of several global geological events such as the Hadley Cell,the Equatorial Upwelling Current,and the Jurassic True Polar Wander.The collision during the evolution of the foreland basin since the Cenozoic led to weak destruction,which was conducive to the preservation of oil and gas.Accordingly,it is be-lieved that the slow drifting and long retention in favorable climate zone of the continent are the critical factors for hydrocarbon enrichment.Moreover,the prospects of hydrocarbon potential in other continents in the Neo-Tethyan were proposed.ZHU Rixiang ZHANG Shuichang WAN Bo ZHANG Wang LI Yong WANG Huajian LUO Beiwei LIU Yuke HE Zhiliang JIN Zhijun 2023Petroleum Exploration and Development2023,50,1:4
17miR-4458 inhibits the epithelial-mesenchymal transition of hepatocellular carcinoma cells by suppressing the TGF-β signaling pathway via targeting TGFBR1显示文摘Hepatocellular carcinoma(HCC)is one of the most lethal cancers in the world.MicroRNAs play a pivotal role in the progression of various cancers.To date,very lttle attention has beerl paid to miR-4458.Therefore,the aim of our study was to explore the function and underlying molecular mech-anism of miR-4458 in HCC.We found that the expression of miR-4458 was reduced in HCC tissues and cell lines.Forced overexpression of miR-4458 inhibited the migration,invasion,and epithelial-mesenchymal transition(EMT)of HCC cells,while downregulation of miR-4458 promoted the aggressive phenotype.Furthermore,transforming growth factor beta receptor 1(TGFBR1),the modulator of the TGF-βsignaling pathway,was verified to be a novel target gene of miR-4458 by dual-luciferase reporter gene assay.Upregulated miR-4458 dramatically abolished TGFBR1 and p-Smad2/3 expression,thus blocking the TGF-βsig naling pathway.Moreover,restoration of TGFBR1 partially rescued the miR-4458-mediated suppressive effect on the migration,invasion,and EMT and reactivated the TGFβsignaling pathway in HCC cells.In summary,our findings first demonstrated a mechanism of miR 4458 in HCC cell migration,invasion,and EMT by regulating the TGFβsignaling pathway via directly targeting TGFBR1.Yuke Zhang Kun Shi Hang Liu Wei Chen Yunhai Luo Xufu Wei Zhongjun Wu 2020Acta Biochimica et Biophysica Sinica2020,52,5:4
18High-entropy perovskite RETa_(3)O_(9) ceramics for high-temperature environmental/thermal barrier coatings显示文摘Four high-entropy perovskite(HEP)RETa_(3)O_(9) samples were fabricated via a spark plasma sintering(SPS)method,and the corresponding thermophysical properties and underlying mechanisms were investigated for environmental/thermal barrier coating(E/TBC)applications.The prepared samples maintained low thermal conductivity(1.50 W·m^(−1)·K^(−1)),high hardness(10 GPa),and an appropriate Young’s modulus(180 GPa),while the fracture toughness increased to 2.5 MPa·m^(1/2).Nanoindentation results showed the HEP ceramics had excellent mechanical properties and good component homogeneity.We analysed the influence of different parameters(the disorder parameters of the electronegativity,ionic radius,and atomic mass,as well as the tolerance factor)of A-site atoms on the thermal conductivity.Enhanced thermal expansion coefficients,combined with a high melting point and extraordinary phase stability,expanded the applications of the HEP RETa_(3)O_(9).The results of this study had motivated a follow-up study on tantalate high-entropy ceramics with desirable properties.Lin CHEN Baihui LI Jun GUO Yuke ZHU Jing FENG 2022Journal of Advanced Ceramics2022,11,4:4
19The N^6-adenine methylation in yeast genome profiled by single-molecule technology显示文摘The most common and abundant DNA modification is 5-methylcytosine(5mC),which has been well-established as an epigenetic mark regulating gene expression in eukaryotes(Jones,2012).Another DNA modification N^6-methyldeoxyadenosine(6mA),previously reported as a widespread DNA methylation in prokaryotes,Zhe Liang Guoliang Yu Jingrong Liu Yuke Geng Jinghui Mao Depeng Wang Jiapeng Zhou Xiaofeng Gu 2018Journal of Genetics and Genomics2018,45,4:3
20METTL5 stabilizes c-Myc by facilitating USP5 translation to reprogram glucose metabolism and promote hepatocellular carcinoma progression显示文摘Background:Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in the world,with a high likelihood of metastasis and a dismal prognosis.The reprogramming of glucosemetabolism is critical in the development ofHCC.TheWarburg effect has recently been confirmed to occur in a variety of cancers,including HCC.However,little is known about the molecular biological mechanisms underlying the Warburg effect in HCC cells.In this study,we sought to better understand how methyltransferase 5,N6-adenosine(METTL5)controls the development of HCC and theWarburg effect.Methods:In the current study,quantitative real-time polymerase chain reaction and Western blotting were used to detect the expression of METTL5 in HCC tissues and cell lines.Several different cell models and animal models were established to determine the role of METTL5 in glucose metabolism reprogramming and the underlying molecularmechanism of HCC.Glutathione-S-transferase pulldown,coimmunoprecipitation,RNA sequencing,non-targeted metabolomics,polysome profiling,and luciferase reporter assays were performed to investigate the molecular mechanisms of METTL5 in HCC cells.Results:We discovered that METTL5 drove glucose metabolic reprogramming to promote the proliferation and metastasis of HCC.Mechanistically,upregulation of METTL5 promoted c-Myc stability and thus activated its downstream glycolytic genes lactate dehydrogenase A(LDHA),enolase 1(ENO1),triosephosphate isomerase 1(TPI1),solute carrier family 2 member 1(SLC2A1),and pyruvate kinase M2(PKM2).The c-Box and ubiquitin binding domain(UBA)regions of ubiquitin specific peptidase 5(USP5)binded to c-Myc protein and inhibited K48-linked polyubiquitination of c-Myc.Further study revealed that METTL5 controled the USP5 translation process,which in turn regulated the ubiquitination of c-Myc.Furthermore,we identified cAMP responsive element binding protein 1(CREB1)/P300 as a critical transcriptional regulator ofMETTL5 that promoted the transcription of METTL5 in HCC.In patient-derived tumor xenograft(PDX)models,adenovirus-mediated knockout of METTL5 had a good antitumor effect and prolonged the survival of PDX-bearing mice.Conclusions:These findings point to a novel mechanism by which CREB1/P300-METTL5-USP5-c-Myc controls abnormal glucose metabolism and promotes tumor growth,suggesting that METTL5 is a potential therapeutic target and prognostic biomarker for HCC.Peng Xia Hao Zhang Haofeng Lu Kequan Xu Xiang Jiang Yuke Jiang Xiangdong Gongye Zhang Chen Jie Liu Xi Chen Weijie Ma Zhonglin Zhang Yufeng Yuan 2023Cancer Communications2023,43,3:3
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