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| 1 | Aberrant translation regulated by METTL1/WDR4-mediated tRNA N7-methylguanosine modification drives head and neck squamous cell carcinoma progression显示文摘Background:Cancer cells selectively promote the translation of oncogenic tran-scripts to stimulate cancer progression.Although growing evidence has revealed that tRNA modifications and related genes participate in this process,their roles in head and neck squamous cell carcinoma(HNSCC)remain largely unchar-acterized.Here,we sought to investigate the function and mechanisms of the transfer RNA(tRNA)N7-methylguanosine(m'G)modification in regulating the occurrence and development of HNSCC.Methods:Cell lost of-function and gain-of function assays,xenograft models,conditional knockout and knockin mouse models were used to study the physi-ological functions of tRNA m'G modification in HNSCC tumorigenesis.tRNA modification and expression profiling,mRNA translation profiling and res-cue assays were performed to uncover the underlying molecular mechanisms.Single-cell RNA sequencing(scRNA seq)was conducted to explore the tumor microenvironment changes.Results:The tRNA.m7G methyltransferase complex components Methyltransferase-like 1(METTL1)/WD repeat domain 4(WDR4)were upregulated in HNSCC and associated with a poor prognosis.Functionally,METTL1/WDR4 promoted HNSCC progression and metastasis in cell-based and transgenic mouse models.Mechanistically,ablation of METTL1 reduced the m'G levels of 16 tRNAS,inhibiting the translation of a subset of oncogenic transcripts,including genes related to the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR)signaling pathway.In addition,chemical modulators of the PI3K/Akt/mTOR signaling pathway reversed the effects of Mettll in mouse HNSCC.Furthermore,scRNA-seq results revealed that Mettll knockout in mouse tumor cells altered the immune landscape and cell-cell interaction between the tumor and stromal compartment.Conclusions:The tRNA m?G methyltransferase METTLI was found to promote the development and malignancy of HNSCC through regulating global mRNA translation,including the PI3K/AKT/mTOR signaling pathway,and found to alter immune landscape.METTLI could be a promising treatment target for HNSCC patients. | Jie Chen Kang Li Jianwen Chen Xiaochen Wang Rongsong Ling Maosheng Cheng Zhi Chen Fangfang Chen Qianting He Shuai Li Caihua Zhang Yizhou Jiang Qianming Chen Anxun Wang Demeng Chen | 2022 | Cancer Communications2022，42，3： | 6 |
| 2 | Super enhancer inhibitors suppress MYC driven transcriptional amplification and tumor progression in osteosarcoma显示文摘Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients. | Demeng Chen Zhiqiang Zhao Zixin Huang Du-Chu Chen Xin-Xing Zhu Yi-Ze Wang Ya-Wei Yan Shaojun Tang Subha Madhavan Weiyi Ni Zhan-peng Huang Wen Li Weidong Ji Huangxuan Shen Shuibin Lin Yi-Zhou Jiang | 2018 | Bone Research2018，6，2： | 5 |
| 3 | Methyltransferase like 13 mediates the translation of Snail in head and neck squamous cell carcinoma显示文摘Methyltransferase like 13(METTL13),a kind of methyltransferase,is implicated in protein binding and synthesis.The upregulation of METTL13 has been reported in a variety of tumors.However,little was known about its potential function in head and neck squamous cell carcinoma(HNSCC)so far.In this study,we found that METTL13 was significantly upregulated in HNSCC at both mRNA and protein level.Increased METTL13 was negatively associated with clinical prognosis.And METTL13 markedly affected HNSCC cellular phenotypes in vivo and vitro.Further mechanism study revealed that METTL13 could regulate EMT signaling pathway by mediating enhancing translation efficiency of Snail,the key transcription factor in EMT,hence regulating the progression of EMT.Furthermore,Snail was verified to mediate METTL13-induced HNSCC cell malignant phenotypes.Altogether,our study had revealed the oncogenic role of METTL13 in HNSCC,and provided a potential therapeutic strategy. | Xiaochen Wang Kang Li Yuehan Wan Fangfang Chen Maosheng Cheng Gan Xiong Ganping Wang Shuang Chen Zhi Chen Jianwen Chen Xiuyun Xu Cheng Wang Liang Peng Demeng Chen | 2021 | International Journal of Oral Science2021，13，3： | 3 |
| 4 | Development of Gesture-Changeable under-actuated Humanoid Robotic Finger显示文摘Robotic fingers,which are the key parts of robot hand,are divided into two main kinds:dexterous fingers and under-actuated fingers.Although dexterous fingers are agile,they are too expensive.Under-actuated fingers can grasp objects self-adaptively,which makes them easy to control and low cost,on the contrary,under-actuated function makes fingers feel hard to grasp things agilely enough and make many gestures.For the purpose of designing a new finger which can grasp things dexterously,perform many gestures and feel easy to control and maintain,a concept called 'gesture-changeable under-actuated' (GCUA) function is put forward.The GCUA function combines the advantages of dexterous fingers and under-actuated fingers:a pre-bending function is embedded into the under-actuated finger.The GCUA finger can not only perform self-adaptive grasping function,but also actively bend the middle joint of the finger.On the basis of the concept,a GCUA finger with 2 joints is designed,which is realized by the coordination of screw-nut transmission mechanism,flexible drawstring constraint and pulley-belt under-actuated mechanism.Principle analyses of its grasping and the design optimization of the GCUA finger are given.An important problem of how to stably grasp an object which is easy to glide is discussed.The force analysis on gliding object in grasping process is introduced in detail.A GCUA finger with 3 joints is developed.Many experiments of grasping different objects by of the finger were carried out.The experimental results show that the GCUA finger can effectively realize functions of pre-bending and self-adaptive grasping,the grasping processes are stable.The GCUA finger excels under-actuated fingers in dexterity and gesture actions and it is easier to control and cheaper than dexterous hands,becomes the third kinds of finger. | ZHANG Wenzeng CHE Demeng CHEN Qiang DU Dong | 2010 | Chinese Journal of Mechanical Engineering2010，23，2： | 3 |
| 5 | Targeting cancer stem cells in squamous cell carcinoma显示文摘Head and neck squamous cell carcinoma(HNSCC)is a highly aggressive tumor and the sixth most common cancer worldwide.Current treatment strategies for HNSCC are surgery,radiotherapy,chemotherapy,immunotherapy or combinatorial therapies.However,the overall 5-year survival rate of HNSCC patients remains at about 50%.Cancer stem cells(CSCs),a small population among tumor cells,are able to self-renew and differentiate into different tumor cell types in a hierarchical manner,similar to normal tissue.In HNSCC,CSCs are proposed to be responsible for tumor initiation,progression,metastasis,drug resistance,and recurrence.In this review,we discuss the molecular and cellular characteristics of CSCs in HNSCC.We summarize current approaches used in the literature for identification of HNSCC CSCs,and mechanisms required for CSC regulation.We also highlight the role of CSCs in treatment failure and therapeutic targeting options for eliminating CSCs in HNSCC. | Demeng Chen Cun-Yu Wang | 2019 | Precision Clinical Medicine2019，2，3： | 2 |
| 6 | Mettl5 mediated 18S rRNA N6-methyladenosine(m^(6)A)modification controls stem cell fate determination and neural function显示文摘Ribosome RNA(rRNA)accounts for more than 80%of the cell's total RNA,while the physiological functions of rRNA modifications are poorly understood.Mutations of 18S rRNA m6A methyltransferase METTL5 cause intellectual disability,microcephaly,and facial dysmorphisms in patients,however,little is known about the underlying mechanisms.In this study,we identified METTL5 protein complex and revealed that METTL5 mainly interacts with RNA binding proteins and ribosome proteins.Functionally,we found that Mettl5 knockout in mESCs leads to the abnormal craniofacial and nervous development.Moreover,using Mettl5 knockout mouse model,we further demonstrated that Mettl5 knockout mice exhibit intellectual disability,recapitulating the human phenotype.Mechanistically,we found that Mettl5 maintains brain function and intelligence by regulating the myelination process.Our study uncovered the causal correlation between mis-regulated 18S rRNA m6A modification and neural function defects,supporting the important physiological functions of rRNA modifications in human diseases. | Lu Wang Yu Liang Rongzhi Lin Qiuchan Xiong Peng Yu Jieyi Ma Maosheng Cheng Hui Han Xiaochen Wang Ganping Wang Fengyin Liang Zhong Pei Demeng Chen Quan Yuan Yi-Zhou Jiang Shuibin Lin | 2022 | Genes & Diseases2022，9，1： | 0 |
| 7 | Dynamic pursuing ecological model concerning the nitrogen cycle in the environment of Chinese mainland显示文摘The paper gives a special dynamic pursuing ecological model on the bio-geochemical cycle of nitrogen in the whole range 9.6 million square kilometers of Chinese mainland, basing on the reservoir-content and flux-rate of nitrogen and among the four spheres: atmosphere, pedosphere, biosphere, and hydrosphere, and the law of bio-geochemical cycle of nitrogen, the model predicted the size of reservoir capacities and fluxes of nitrogen in each sphere. Through tested and verified, the model was proven reasonable and reliable. | Kang Demeng and Chen LidingResearch Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China | 1993 | Journal of Environmental Sciences1993，5，1： | 0 |
| 8 | Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma显示文摘Pleomorphic adenoma(PA)is the most common benign tumour in the salivary gland and has high morphological complexity.However,the origin and intratumoral heterogeneity of PA are largely unknown.Here,we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations,three recapitulating the epithelial states of the normal parotid gland,and two PA-specific epithelial cell(PASE)populations unique to tumours.Then,six subgroups of PASE cells were identified,which varied in epithelium,bone,immune,metabolism,stemness and cell cycle signatures.Moreover,we revealed that CD36+myoepithelial cells were the tumour-initiating cells(TICs)in PA,and were dominated by the PI3K-AKT pathway.Targeting the PI3K-AKT pathway significantly inhibited CD36+myoepithelial cell-derived tumour spheres and the growth of PA organoids.Our results provide new insights into the diversity and origin of PA,offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment. | Xiuyun Xu Jiaxiang Xie Rongsong Ling Shengqi Ouyang Gan Xiong Yanwen Lu Bokai Yun Ming Zhang Wenjin Wang Xiqiang Liu Demeng Chen Cheng Wang | 2023 | International Journal of Oral Science2023，15，3： | 0 |
| 9 | Natural history and cycle threshold values analysis of COVID-19 in Xiamen City,China显示文摘Objective:This study elaborated the natural history parameters of Delta variant,explored the differences in detection cycle thresholds(Ct)among cases.Methods:Natural history parameters were calculated based on the different onset time and exposure time of the cases.Intergenerational relationships between generations of cases were calculated.Differences in Ct values of cases by gender,age,and mode of detection were analyzed statistically to assess the detoxification capacity of cases.Results:The median incubation period was 4 days;the detection time for cases decreased from 25 to 7 h as the outbreak continued.The average generation time(GT),time interval between transmission generations(TG)and serial interval(SI)were 3.6±2.6 days,1.67±2.11 days and 1.7±3.0 days.Among the Ct values,we found little differences in testing across companies,but there were some differences in the gender of detected genes.The Ct values continuous to decreased with age,but increased when the age was greater than 60.Conclusion:This epidemic was started from aggregation of factories.It is more reasonable to use SI to calculate the effective reproduction number and the time-varying reproduction number.And the analysis of Ct values can improve the positive detection rate and improve prevention and control measures. | Bin Deng Weikang Liu Zhinan Guo Li Luo Tianlong Yang Jiefeng Huang Buasiyamu Abudunaibi Yidun Zhang Xue Ouyang Demeng Wang Chenghao Su Tianmu Chen | 2022 | Infectious Disease Modelling2022，7，3： | 0 |
| 10 | Sox9^(+) cells are required for salivary gland regeneration after radiation damage via the Wnt/β-catenin pathway显示文摘Radiotherapy for head and neck cancer can cause serious side effects, including severe damage to the salivary glands, resulting in symptoms such as xerostomia, dental caries, and oral infection. Because of the lack of long-term treatment for the symptoms of xerostomia, current research has focused on finding endogenous stem cells that can differentiate into various cell lineages to replace lost tissues and restore functions. Here, we report that Sox9^(+)cells can differentiate into various salivary epithelial cell lineages under homeostatic conditions. After ablating Sox9^(+) cells, the salivary glands of irradiated mice showed more severe phenotypes and the reduced proliferative capacity. Analysis of online single-cell RNAsequencing data reveals the enrichment of the Wnt/β-catenin pathway in the Sox9^(+) cell population.Furthermore, treatment with a Wnt/β-catenin inhibitor in irradiated mice inhibits the regenerative capability of Sox9^(+) cells. Finally, we show that Sox9^(+) cells are capable of forming organoids in vitro and that transplanting these organoids into salivary glands after radiation partially restored salivary gland functions.These results suggest that regenerative therapy targeting Sox9^(+) cells is a promising approach to treat radiation-induced salivary gland injury. | Xiuyun Xu Gan Xiong Ming Zhang Jiaxiang Xie Shuang Chen Kang Li Jingting Li Yong Bao Cheng Wang Demeng Chen | 2022 | Journal of Genetics and Genomics2022，49，3： | 0 |
| 11 | RNPS1 stabilizes NAT10 protein to facilitate translation in cancer via tRNA ac^(4)C modification显示文摘Existing studies have underscored the pivotal role of N-acetyltransferase 10(NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma(HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1(RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6(ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac^(4)C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel t RNA-ac^(4)C modification sites, thereby providing a potent sequencing tool for tRNAac^(4)C research. Our findings expand the repertoire of tRNA ac^(4)C modifications and identify a role of tRNA ac^(4)C in the regulation of mRNA translation in HNSCC. | Xiaochen Wang Rongsong Ling Yurong Peng Weiqiong Qiu Demeng Chen | 2024 | International Journal of Oral Science2024，16，1： | 0 |
| 12 | Structural basis of humanα7 nicotinic acetylcholine receptor activation显示文摘Dear Editor,Nicotinic acetylcholine receptors(nAChRs)are a class of pentameric ligand-gated ion channels(pLGICs)widely expressed in nervous system.nAChRs function as neurotransmitter receptors that respond to endogenous acetylcholine and choline,modulating neuronal excitability and synaptic communication.The homomericα7 nAChR is among the most abundant subtypes of nAChR in the brain.Dysfunction ofα7 is found to be associated with several neuropsychiatric and neurologic disorders,including schizophrenia and Alzheimer’s disease.1,2 Stimulation ofα7 has been reported to improve attention,cognitive performance,and neuronal resistance to injury.Therefore,agonists and positive allosteric modulators(PAMs)ofα7 have become hot candidates in the drug development for the treatment ofα7-related diseases.3,4 EVP-6124(abbreviated as EVP)is a high-affinityα7-selective agonist.5 PNU-120596(abbreviated as PNU)is the first reportedα7-selective PAM that could increase the peak current of the receptor evoked by agonists and delay channel desensitization.6 Both EVP and PNU are in clinical trials for the treatment of Alzheimer’s disease,schizophrenia,and cognitive impairment.Despite the significance ofα7 in physiology and pharmacology,the mechanisms underlying the activation ofα7 upon agonist and/or PAM binding remain elusive.Little is known about the structural basis of the higher selectivity of EVP and PNU forα7,which would be highly valuable for rational drug development targeting the receptor.Herein,we report the structures of full-length humanα7 in apo,EVP-bound and EVP/PNU-bound states at 3.18,2.85 and 3.02Å,respectively(Fig.1a–c;Supplementary information,Figs.S1–S4 and Table S1). | Yue Zhao Sanling Liu Yingxin Zhou Mengge Zhang Haopeng Chen HEric Xu Demeng Sun Lei Liu Changlin Tian | 2021 | Cell Research2021，31，6： | 0 |
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