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| 1 | METTL5 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 | 2023 | Cancer Communications2023,43,3: | 3 |
| 2 | Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis显示文摘RNAs are involved in the crucial processes of disease progression and have emerged as powerful therapeutic targets and diagnostic biomarkers.However,efficient delivery of therapeutic RNA to the targeted location and precise detection of RNA markers remains challenging.Recently,more and more attention has been paid to applying nucleic acid nanoassemblies in diagnosing and treating.Due to the flexibility and deformability of nucleic acids,the nanoassemblies could be fabricated with different shapes and structures.With hybridization,nucleic acid nanoassemblies,including DNA and RNA nanostructures,can be applied to enhance RNA therapeutics and diagnosis.This review briefly introduces the construction and properties of different nucleic acid nanoassemblies and their applications for RNA therapy and diagnosis and makes further prospects for their development. | Mengnan Zhao Rujing Wang Kunmeng Yang Yuhong Jiang Yachen Peng Yuke Li Zhen Zhang Jianxun Ding Sanjun Shi | 2023 | Acta Pharmaceutica Sinica B2023,13,3: | 2 |
| 3 | Design and Analysis of Low-power 10-Transislor Full Adders using Novel XOR-XNOR Gates 显示文摘 | Hungtien Bui Yuke Wang Yingtao Jiang | 2002 | IEEE Transactions on Circuits and Systems2002,49,1: | 1 |
| 4 | Design and analysis of low--power 10--transislor full adders using novel XOR--XNOR gates 显示文摘 | Bui Hungtien Wang Yuke Jiang Yingtao | 2002 | IEEE Transactions on Circuits and systems2002,49,1: | 1 |
| 5 | Seryl tRNA synthetase cooperates with POT1 to regulate telomere length and cellular senescence显示文摘Deregulated telomere length is a causative factor in many physiological and pathological processes,including aging and cancer.Many studies focusing on telomeres have revealed important roles for cooperation between the Shelterin protein complex and telomerase in maintaining telomere length.However,it remains largely unknown whether and how aging-related stresses,such as deregulated protein homeostasis,impact telomere length.Here,we explored the possible roles of aminoacyl tRNA synthetases(AARSs),key enzymes catalyzing the first reactions in protein synthesis,in regulating telomere length and aging.We selected seryl tRNA synthetase(SerRS)since our previous studies discovered expanded functions of SerRS in the nucleus in addition to its canonical cytoplasmic role in protein synthesis.In this study,we revealed that overexpression of SerRS promoted cellular senescence and inhibited the growth of cervical tumor xenografts in mice by triggering the senescence of tumor cells.In the nucleus,SerRS directly bound to telomeric DNA repeats and tethered more POT1 proteins to telomeres through a direct interaction between the UNE-S domain of SerRS and the OB1 domain of POT1.We further demonstrated that SerRS-induced enrichment of POT1 prevented the recruitment of telomerase to telomeres,resulting in progressive telomere shortening.Our data suggested a possible molecular link between protein synthesis and telomere length control,the deregulation of which may be associated with aging and cancer. | Yingxi Li Xiyang Li Mei Cao Yuke Jiang Jie Yan Ze Liu Rongcun Yang Xu Chen Peiqing Sun Rong Xiang Longlong Wang Yi Shi | 2019 | Signal Transduction and Targeted Therapy2019,4,1: | 1 |
| 6 | Structural and superconducting properties of LaFeAs_(1-x)Sb_xO_(1-y)F_y显示文摘We report the antimony(Sb) doping effect in a prototype system of iron-based superconductors LaFeAsO1-yFy(y=0,0.1,0.15).X-ray powder diffraction indicates that the lattice parameters increase with Sb content within the doping limit.Rietveld structural refinements show that,with the partial substitution of Sb for As,the thickness of the Fe2As2 layers increases significantly,whereas that of the La2O2 layers shrinks simultaneously.So a negative chemical pressure is indeed 'applied' to the superconducting-active Fe2As2 layers,in contrast to the effect of positive chemical pressure by the phosphorus doping.Electrical resistance and magnetic susceptibility measurements indicate that,while the Sb doping hardly influences the SDW anomaly in LaFeAsO,it recovers SDW order for the optimally-doped sample of y=0.1.In the meantime,the superconducting transition temperature can be raised up to 30 K in LaFeAs1-xSbxO1-yFy with x=0.1 and y=0.15.The Sb doping effects are discussed in term of both J1-J2 model and Fermi Surface(FS) nesting scenario. | WANG Cao,MA ZhiFeng,JIANG Shuai,LI YuKe,XU ZhuAn & CAO GuangHan* Department of Physics,Zhejiang University,Hangzhou 310027,China | 2010 | Science China(Physics,Mechanics & Astronomy)2010,53,7: | 1 |
| 7 | Flexoelectric-induced photovoltaic effects and tunable photocurrents in flexible LaFeO_(3) epitaxial heterostructures显示文摘By engineering strain gradients in dielectrics,the flexoelectric effect can be created,which yields interesting physical properties via electromechanical coupling.Here,we report flexoelectric-induced photovoltaic effects in centrosymmetric LaFeO_(3) thin-film heterostructures grown on flexible mica sub-strates,in which partial relaxation of lattice-mismatch strain against LaAlO_(3) stretching layers results in giant strain gradients and pronounced electrical polarizations.The flexoelectric polarization modulates band alignment and leads to significant photovoltaic effects with a short-circuit current density of~0.4 mA/cm^(2) and an open circuit voltage of~-0.45 V in Pt/LaFeO_(3)/LaNiO_(3) devices.In addition,by con-cavely/convexly bending the mica substrate,mechanical strain gradients give rise to bi-directionally tunable photocurrents,in which continuously change of short-circuit current density with a magni-tude of~100% and good reproducibility in repetitive bending operations are observed in the Pt/LaFeO_(3)/LaNiO_(3) devices.The present work demonstrates an approach to design self-powered photoelectric de-vices with an electromechanical degree of freedom based on the flexoelectric effect in flexible thin-film heterostructures. | Zhizheng Jiang Zhiyu Xu Zhongnan Xi Yihao Yang Ming Wu Yuke Li Xiang Li Qianying Wang Chen Li Di Wu Zheng Wen | 2022 | Journal of Materiomics2022,8,2: | 0 |