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| 1 | Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility显示文摘Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF. | Lijun Ding Guijun Yan Bin Wang Lu Xu Yan Gu Tong Ru Xiaoying Cui Lei Lei Jingyu Liu Xiaoqiang Sheng Bin Wang Chunxue Zhang Yanjun Yang Ruiwei Jiang Jianjun Zhou Na Kong Feifei Lu Huaijun Zhou Yannan Zhao Bing Chen Yali Hu Jianwu Dai Haixiang Sun | 2018 | Science China(Life Sciences)2018，61，12： | 43 |
| 2 | A highly homozygous and parthenogenetic human embryonic stem cell line derived from a one-pronuclear oocyte following in vitro fertilization procedure显示文摘因为他们的人的白血球抗原(HLA ) haplotype 将强烈增加与房间线的相对更小的队为某些人口匹配的度,同型结合的人的胚胎的干细胞(hESCs ) 被认为是为 hESC 银行的更好的房间来源。同型结合的 hESCs 能从单性生殖的胚胎被产生,但是仅仅异质接合的 hESCs 用当前的策略被建立了没有第二极的身体挤出,人工地激活卵母细胞。这里,我们在 vitro 授精处理从 one-pronuclear 卵母细胞追随者例程报导一根人的同型结合的转换字符线(chHES-32 ) 的第一成功的推导。chHES-32 房间与正常 hESCs 表示普通标记和基因。他们处于一个无差别的状态被宣传超过一年(>P50 ) 了并且维持了 46 的稳定的 karyotype, XX。当在 vivo 并且在 vitro 区分了时, chHES-32 房间能从所有三胚胎的细菌层形成衍生物。五父亲一般地表示的印的基因和他们与卵母细胞施主相同的 HLA 遗传型的几乎无法发现的表示显示了他们的单性生殖的起源。用染色体宽的单个核苷酸的多型性分析并且 DNA 采指纹, chHES-32 房间的 homozygosity 进一步被证实。结果显示“讨厌”的 one-pronuclear 卵母细胞可能是为人的同型结合、单性生殖的转换字符的潜在的来源,并且为从单性生殖的 haploid 卵母细胞获得同型结合的 hESC 线建议了其他的策略。 | Ge Lin | 2007 | Cell Research2007，17，12： | 15 |
| 3 | Single-cell RNA-seq reveals the diversity of trophoblast subtypes and patterns of differentiation in the human placenta显示文摘胎盘为成功的怀孕和胎儿和怀孕女人的健康是关键的。然而,人的 trophoblast 系怎么被调整,包括胎盘的房间的分类,子类型糟糕被理解。这里,我们在排序的胎盘的房间上执行了定序的单个房间的 RNA (RNA-seq ) 从第一三个月并且秒三个月人胎盘。已知的 cytotrophoblast 房间(CTB ) 的房间的新子类型, extravillous trophoblast 房间(EVT ) , Hofbauer 房间,和间充质的 stromal 房间被识别, cell-type-specific 基因签名被定义。机能上地,这研究揭示了人的胎盘的许多以前未知的功能。尤其是, 102 多肽荷尔蒙基因被发现被胎盘的房间的各种各样的子类型表示,它在调整母亲的生理学的胎儿的生长和改编到怀孕建议建筑群和这些荷尔蒙的重要角色。这些结果在单个房间的分辨率记录人的胎盘的 trophoblast 区别并且因此在怀孕的早阶段期间推进我们人的胎座式的理解。 | Yawei Liu Xiaoying Fan Rui Wang Xiaoyin Lu Yan-Li Dang Huiying Wang Hai-Yan Lin Cheng Zhu Hao Ge James C. Cross Hongmei Wang | 2018 | Cell Research2018，28，8： | 15 |
| 4 | Additive manufacturing of high-strength CrMnFeCoNi high-entropy alloys-based composites with WC addition显示文摘Laser melting deposition with WC addition has been developed to fabricate high-strength CrMnFeCoNibased high-entropy alloys-based composites.By this technique,a microstructure of compact refined equiaxed grains can be achieved,and the tensile strength can be remarkably improved.The sample with 5 wt%WC addition shows a promising mechanical performance with a tensile strength of 800 MPa and an elongation of 37%.The improvement in mechanical property may be attributed to the formation of Cr(23)C6 reinforcement precipitates,which could promote the heterogeneous nucleation of grains and hinder the propagation of slip bands. | Jinfeng Li Shuo Xiang Hengwei Luan Abdukadir Amar Xue Liu Siyuan Lu Yangyang Zeng Guomin Le Xiaoying Wang Fengsheng Qu Chunli Jiang Guannan Yang | 2019 | Journal of Materials Science & Technology2019，35，11： | 13 |
| 5 | Effect of warm bladder irrigation fluid for benign prostatic hyperplasia patients on perioperative hypothermia, blood loss and shiver: A meta-analysis显示文摘Objective:To find out whether warm bladder irrigation fluid can decrease the occurrence of perioperative hypothermia,blood loss and shiver in patients treated with benign prostatic hyperplasia(BPH).Method:A comprehensive literature review and meta-analysis that included randomized controlled trials(RCTs)related to temperature of irrigation fluid in the perioperative treatment for BPH was taken by researchers.The relevant literature were searched in Chinese database,such as Retrieval Chinese Journal Full-text Database,VIP Journal Database,Wanfang database,as well as in English search engine and database,including Embase,Cochrane and Medline till January 2018.The study quality was assessed by recommended standards from Cochrane Handbook(version 5.1.0).Results:A total of 28 RCTs and 3858 patients were included.The results showed that the incidences of shiver(risk ratio[RR]Z 0.32,95%confidence interval[CI]:0.28e0.36,p<0.001,I^2 Z 0%)and hypothermia(RR Z 0.36,95%CI:0.21e0.59,p<0.001,I^2 Z 67%)in the group of warm irrigation fluid were lower than the group having room-temperature fluid.Room-temperature irrigation fluid group caused a greater drop in body temperature compared to warm irrigation fluid group(p<0.001,I^2 Z 96%).We performed a narrative descriptive statistics only because of substantial heterogeneity.Conclusions:Warm bladder irrigation fluid can decrease the drop of body temperature and the incidence of hypothermia and shiver during and after the operation for BPH.Warm irrigation fluid should be considered as a standard practice in BPH surgeries. | Jie Cao Xia Sheng Yan Ding Lingjuan Zhang Xiaoying Lu | 2019 | Asian Journal of Urology2019，6，2： | 12 |
| 6 | Current perspectives on in vitro maturation and its effects on oocyte genetic and epigenetic profiles显示文摘In vitro maturation(IVM), the maturation in culture of immature oocytes, has been used in clinic for more than 20 years.Although IVM has the specific advantages of low cost and minor side effects over controlled ovarian stimulation, the prevalence of IVM is less than 1% of routine in vitro fertilization and embryo transfer techniques in many reproductive centers. In this review, we searched the MEDLINE database for all full texts and/or abstract articles published in English with content related to oocyte IVM mainly between 2000 and 2016. Many different aspects of the IVM method may influence oocyte potential,including priming, gonadotrophin, growth factors, and culture times. The culture conditions of IVM result in alterations in the oocyte or cumulus cell transcriptome that are not observed under in vivo culture conditions. Additionally, epigenetic modifications, such as DNA methylation or acetylation, are also different between in vitro and in vivo cultured oocytes. In sum,current IVM technique is still not popular and requires more systematic and intensive research to improve its effects and applications. This review will help point our problems, supply evidence or clues for future improving IVM technique, thus assist patients for fertility treatment or preservation as an additional option. | Cuiling Lu Yaoyao Zhang Xiaoying Zheng Xueling Song Rui Yang Jie Yan Huailiang Feng Jie Qiao | 2018 | Science China(Life Sciences)2018，61，6： | 10 |
| 7 | One-step disposal of Cr (Ⅵ)-bearing wastewater by natural pyrrhotite显示文摘Cr(Ⅵ)-bearing wastewater can be treated by natural pyrrhotite which is used for reductant to reduce Cr(Ⅵ) and precipitant to precipitate Cr(Ⅲ) simultaneously. The disposal products can be divided into three parts in the beakers, namely supernatant in the upper part, the yellowish colloidal precipitates in the middle part and the pyrrhotite in the lower part. The content of total Cr=Cr(Ⅵ)+Cr(Ⅲ) in the supernatant liquid is 0.06 mg/L, which is lower than 1.5 mg/L of the discharge standard of China and near to 0.05 mg/L of the standard of potable water. This one-step disposal composing of both reduction and precipitation which is traditionally divided into two independent steps called reducing technology and precipitating technology respectively. The new method is of obvious economic advantage and favourable to decreasing surplus mud derived from adding Ca(OH)2 to precipitate Cr(Ⅲ) traditionally so as to avoid recontamination. In fact, sodium sulfite (Na2SO3) used in disposal of Cr(Ⅵ) was | LU Anhuai, CHEN Jie, SHI Junxian, LU Xiaoying, TANG Junli & GUO Min1. Departmenl of Geology, Peking University, Beijing 100871, China 2. National Laboratory of Mineral and Rock Materials, China University of Geosciences, Beijing 100083, China (e-mail: luanhuai | 2000 | Chinese Science Bulletin2000，45，17： | 9 |
| 8 | DNA methylation and chromatin accessibility profiling of mouse and human fetal germ cells显示文摘染色质改变为人的初发的细菌房间的 epigenetic reprogramming 是重要的。然而,全面染色质状态还没为人的胎儿的细菌房间(FGC ) 被分析了。这里,我们使用 nucleosome 占有和 methylation 定序方法在人和老鼠在胎儿的细菌房间开发期间在一系列关键时间点分析染色体宽的染色质可接近性和 DNA methylome。我们在人和老鼠 FGC 发现 116 887 和 137 557 个弄空 nucleosome 的区域(NDR ) ,盖住 germline 特定、高度有活力的规章的 genomic 元素的一个大集合,例如 enhancers。而且,我们发现远侧的 NDR 在人的 FGC 为象 NANOG , SOX17 , AP2 和 OCT4 那样的 pluripotency 和细菌房间主人管理者的有约束力的主题明确地被充实,显示在pluripotency相关的基因和细菌之间的精细的规章的平衡的存在在人的 FGC 的房间特定的基因,并且为在 vivo 的细菌房间开发的这些基因的功能的意义。我们的工作为把提供一张全面、高分辨率的路线图染色质状态转变动力学在人和老鼠 FGC 的 epigenomic reprogramming 期间。 | Hongshan Guo Boqiang Hu Liying Yan Jun Yong Yan Wu Yun Gao Fan Guo Yu Hou Xiaoying Fan Ji Dong Xiaoye Wang Xiaohui Zhu Jie Yan Yuan Wei Hongyan Jin Wenxin Zhang Lu Wen FuchouTang Jie Qiao | 2017 | Cell Research2017，27，2： | 9 |
| 9 | Embryonic endothelial evolution towards first hematopoietic stem cells revealed by single-cell transcriptomic and functional analyses显示文摘Hematopoietic stem cells(HSCs)in adults are believed to be born from hemogenic endothelial cells(HECs)in mid-gestational embryos.Due to the rare and transient nature,the HSC-competent HECs have never been stringently identified and accurately captured,let alone their genuine vascular precursors.Here,we first used high-precision single-cell transcriptomics to unbiasedly examine the relevant EC populations at continuous developmental stages with intervals of 0.5 days from embryonic day(E)9.5 to E11.0.As a consequence,we transcriptomically identified two molecularly different arterial EC populations and putative HSCprimed HECs,whose number peaked at El 0.0 and sharply decreased thereafter,in the dorsal aorta of the aorta-gonadmesonephros(AGM)region.Combining computational prediction and in vivo functional validation,we precisely captured HSCcompetent HECs by the newly constructed Neurl3-EGFP reporter mouse model,and realized the enrichment further by a combination of surface markers(Procr+Kit+CD44+,PK44).Surprisingly,the endothelial-hematopoietic dual potential was rarely but reliably witnessed in the cultures of single HECs.Noteworthy,primitive vascular ECs from E8.0 experienced two-step fate choices to become HSC-primed HECs,namely an Initial arterial fate choice followed by a hemogenic fate conversion.This finding resolves several previously observed contradictions.Taken together,comprehensive understanding of endothelial evolutions and molecular programs underlying HSC-primed HEC specification in vivo will facilitate future investigations directing HSC production in vitro. | Siyuan Hou Zongcheng Li Xiaona Zheng Yun Gao Ji Dong Yanli Ni Xiaobo Wang Yunqiao Li Xiaochen Ding Zhilin Chang Shuaili Li Yuqiong Hu Xiaoying Fan Yu Hou Lu Wen Bing Liu Fuchou Tang Yu Lan | 2020 | Cell Research2020，30，5： | 8 |
| 10 | An antiretroviral regimen containing 6 months of stavudine followed by long-term zidovudine for first-fine HIV therapy is optimal in resource-limited settings: a prospective, multicenter study in China显示文摘 | Li Taisheng Guo Fuping Li Yijia Zhang Chengda Han Yang Lye Wei He Yun Lu Hongzhou Xie Jing Huang Aiqiong Li Yanling Tang Xiaoping Wang Hui Zhang Tong Gao Guiju Lei Junkang Zhang Xiaoying Wu Xinhua Sun Yongtao Bai Jinsong Luo Ling Wang Huanlmg | 2014 | Chinese Medical Journal2014，，1： | 6 |
| 11 | 胃食管反流病:内镜评估与治疗方面的革新显示文摘内镜技术的创新为胃食管反流病(GERD)的诊治带来了巨大进步。作为世界上最常见的胃肠疾病之一,GERD一直是内镜介入治疗的前沿。目前,GERD的初步诊断是基于症状和质子泵抑制剂(PPI)初期治疗有效,但这对治疗策略的指导价值有限。然而,内镜检查和病理活检可直接观察和判断食管的异常结构和病理生理损伤;同时,内镜治疗的出现给PPI治疗依从性较差或治疗反应不佳以及不适合行胃底折叠抗反流手术的患者提供了新的治疗选择。本综述对内镜检查和活检在经过恰当的抗反流药物治疗后持续存在GERD相关临床表现的患者中的应用情况进行了概述,并介绍了目前内镜治疗GERD的各项新技术及其优缺点。今后的研究需要对GERD患者进行分层研究,并力图阐明该疾病的主要病理生理机制。 | Sheng Chen Feng Du Changqing Zhong Caifang Liu Xiaoying Wang Yan Chen Gang Wang Xiaopei Gao Lu Zhang Lianyong Li Wei Wu | 2021 | Gastroenterology Report2021，9，5： | 4 |
| 12 | Ectopic expression of fungal EcGDH improves nitrogen assimilation and grain yield in rice显示文摘NADP(H)-dependent glutamate dehydrogenases(GDH) in lower organisms have stronger ammonium affinity than those in higher plants. Here we report that transgenic rice overexpressing the EcGDH from Eurotium cheralieri exhibited significantly enhanced aminating activities. Hydroponic and field tests showed that nitrogen assimilation efficiency and grain yields were markedly increased in these transgenic plants, especially at the low nitrogen conditions.These results suggest that EcGDH may have potential to be used to improve nitrogen assimilation and grain yield in rice. | Dongying Tang Yuchong Peng Jianzhong Lin Changqing Du Yuanzhu Yang Dan Wang Cong Liu Lu Yan Xiaoying Zhao Xia Li Liangbi Chen Xuanming Liu | 2018 | Journal of Integrative Plant Biology2018，60，2： | 4 |
| 13 | Silicon-based microelectrode arrays for stimulation and signal recording of in vitro cultured neurons显示文摘Microelectrode arrays (MEAs) for stimulation and signal recording of in vitro cultured neurons are presented.Each MEA is composed of 60 independent electrodes with 59 working ones and one reference one.These electrodes are divided into 30 pairs.Through each pair of electrodes,four independent states can be realized to define the accessing modes of neurons cultured on the surface of the electrodes.A total MEA covers an area of 10 mm×10 mm.MEAs are fabricated in a silicon-based semiconductor process.An implemented MEA is bonded on a specially designed printed-circuit-board (PCB) and surrounded by a culture chamber.An impedance measurement has been made to verify the electrical characteristics of MEAs.The surface was modified to enhance the biocompatibility.A series of PC12 cells culture experiments validates the effectiveness of the modification.An extracellular signal recording experiment with acetylcholine (Ach) as a stimulant has been carried out,and the results show the feasibility of MEAs for extracellular action potential recording.Extracellular electrical stimulation and recording experiments have been carried out too.They indicate that MEAs can be used for extracellular stimulation,recording,simultaneous stimulation and recording,and isolation of PC12 cells network cultured in vitro. | PAN HaiXian LU XiaoYing WANG ZhiGong REN TianLing FANG Tao ZHANG Jie ZHOU ChangJian WANG LiGang | 2011 | Science China(Information Sciences)2011，54，10： | 2 |
| 14 | Small interfering RNA delivery to the neurons near the amyloid plaques for improved treatment of Alzheimer’s disease显示文摘Gene therapy represents a promising treatment for the Alzheimer’s disease(AD). However,gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood–brain barrier(BBB)penetration and QSH peptide for β-amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against β-site amyloid precursor protein-cleaving enzyme 1(BACE1), the rate-limiting enzyme of Aβ production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the Aβ deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels,as well as Aβ and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome. | Qian Guo Xiaoyao Zheng Peng Yang Xiaoying Pang Kang Qian Pengzhen Wang Shuting Xu Dongyu Sheng Liuchang Wang Jinxu Cao Wei Lu Qizhi Zhang Xinguo Jiang | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 2 |
| 15 | Multiplexed intracellular detection based on dual-excitation/dualemission upconversion nanoprobes显示文摘Multiplexed intracellular detection is desirable in biomedical sciences for its higher eficiency and accuracy compared to the single-analyte detection.However,it is very challenging to construct nanoprobes that possess multiple fluorescent signals to recognize the different intracellular species synchronously.Herein,we proposed a novel dual-excitation/dual-emission upconversion strategy for multiplexed detection through the design of upconversion nanoparticles(UCNP)loaded with two dyes for sensitization and quenching of the upconversion luminescence(UCL),respectively.Based on the two independent energy transfer processes of near-infrared(NIR)dye IR845 to UCNP and UCNP to visible dye PAPS-Zn,CIO-and Zn2+were simultaneously detected with a limit of detection(LOD)of41.4 and 10.5 nM,respectively.By tilizing a purpose built 830/980 nm dual-laser confocal microscope,both intrinsic and exogenous CIO and Zn2+in live MCF-7 cells have been accurately quantified.Such dual-excitation/dual-emission ratiometric UCL detection mode enables not only monitoring multiple intracellular analytes but also eliminating the detection deviation caused by inhomogeneous probe distribution in cells.Through modulation of NIR dye and visible dye with other reactive groups,the nanoprobes can be extended to analyze various intraellular species,which provides a promising tool to study the biological activities in live cells and diagnose diseases. | Jianxi Ke Shan Lu Zhuo Li Xiaoying Shang Xingjun Li Renfu Li Datao Tu Zhuo Chen Xueyuan Chen | 2020 | Nano Research2020，13，7： | 2 |
| 16 | Comprehensive lipidomics in apoM^(-/-) mice reveals an overall state of metabolic distress and attenuated hepatic lipid secretion into the circulation显示文摘Apolipoprotein M(apoM) participates in both high-density lipoprotein and cholesterol metabolism. Little is known about how apo M affects lipid composition of the liver and serum. In this study, we systemically investigated the effects of apo M on liver and plasma lipidomes and how apo M participates in lipid cycling, via apo M knockout in mice and the human SMMC-7721 cell line. We used integrated mass spectrometry-based lipidomics approaches to semiquantify more than 600 lipid species from various lipid classes, which include free fatty acids, glycerolipids, phospholipids, sphingolipids, glycosphingolipids, cholesterol, and cholesteryl esters(CEs), in apo M^(-/-)mouse. Hepatic accumulation of neutral lipids, including CEs, triacylglycerols, and diacylglycerols, was observed in apo M^(-/-)mice;while serum lipidomic analyses showed that, in contrast to the liver, the overall levels of CEs and saturated/monounsaturated fatty acids were markedly diminished. Furthermore, the level of Apo B-100 was dramatically increased in the liver, whereas significant reductions in both Apo B-100 and low-density lipoprotein(LDL) cholesterol were observed in the serum of apo M^(-/-)mice, which indicated attenuated hepatic LDL secretion into the circulation. Lipid profiles and proinflammatory cytokine levels indicated that apo M^(-/-)leads to hepatic steatosis and an overall state of metabolic distress. Taken together, these results revealed that apo M knockout leads to hepatic steatosis, impaired lipid secretion, and an overall state of metabolic distress. | Yuanping Shi Sin Man Lam Hong Liu Guanghua Luo Jun Zhang Shuang Yao Jie Li Lu Zheng Ning Xu Xiaoying Zhang Guanghou Shui | 2020 | Journal of Genetics and Genomics2020，47，9： | 2 |
| 17 | Hepatic steatosis exacerbated by endoplasmic reticulum stress-mediated downregulation of FXR in aging mice显示文摘 | Xuelian Xiong Xiaolin Wang Yan Lu E. Wang Zhijian Zhang Jian Yang Huijie Zhang Xiaoying Li | 2013 | Journal of Hepatology2013，，： | 2 |
| 18 | Heterogeneity in endothelial cells and widespread venous arterialization during early vascular development in mammals显示文摘Arteriogenesis rather than unspecialized capillary expansion is critical for restoring effective circulation to compromised tissues in patients.Deciphering the origin and specification of arterial endothelial cells during embryonic development will shed light on the understanding of adult arteriogenesis.However,during early embryonic angiogenesis,the process of endothelial diversification and molecular events underlying arteriovenous fate settling remain largely unresolved in mammals.Here,we constructed the single-cell transcriptomic Iandscape of vascular endothelial cells(VECs)during the time window for the occurrenee of key vasculogenic and angiogenic events in both mouse and human embryos.We uncovered two distinct arterial VEC types,the major artery VECs and arterial plexus VECs,and un expectedly diverge nt arteriove nous characteristics among VECs that are located in morphologically undistinguishable vascular plexus intra-embryonically.Using computational prediction and further lineage tracing of venous-featured VECs with a newly developed Nr2f2^(CrexER) | Siyuan Hou Zongcheng Li Ji Dong Yun Gao Zhilin Chang Xiaochen Ding Shuaili Li Yunqiao Li Yang Zeng Qian Xin Baihan Wang Yanli Ni Xiaowei Ning Yuqiong Hu Xiaoying Fan Yu Hou Xianlong Li Lu Wen Bin Zhou Bing Liu Fuchou Tang Yu Lan | 2022 | Cell Research2022，32，4： | 2 |
| 19 | Algebraic Properties of Toeplitz Operators on the Harmonic Bergman Space显示文摘In this paper, we first investigate the finite-rank product problem of several Toeplitz operators with quasihomogeneous symbols on the harmonic Bergman space. Next, we characterize finite rank commutators and semi-commutators of two Toeplitz operators with quasihomogeneous symbols. | Jingyu YANG Yufeng LU Xiaoying WANG | 2016 | Journal of Mathematical Research with Applications2016，36，4： | 2 |
| 20 | Targeting EZH1/2 induces cell cycle arrest and inhibits cell proliferation through reactivation of p57CDKN1C and TP53INP1 in mantle cell lymphoma显示文摘Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexpression by immunohistochemistry and correlated them to clinical outcome in 41 MCL patients.Quantitative real-time PCR and Western blot were applied to confirm the level of EZH1 and EZH2 in well-characterized MCL cell lines which were compared to those of na?ve B cells.Then we manipulated the expression of EZH1 and EZH2 in MCL cells using CRISPR/Cas9 system to directly investigate their functional roles in MCL.We also evaluated the effect of two small molecule selective inhibitors, EPZ005687 and UNC1999, on MCL cell proliferation, cell cycle distribution and apoptosis in vitro.Finally, we performed RNA-sequencing(RNA-Seq) and Chromatin immunoprecipitation(ChIP) assay to further gain insight into the underlying molecular mechanisms.Results: We found that EZH2 protein is overexpressed in approximately half of this cohort of MCL cases.More importantly, the overexpression of EZH2 is associated with poor OS in the patients.Nevertheless, simple EZH2 depletion in vitro has little impact on the viability of MCL cells, predominantly because of the consequent up-regulation of EZH1.Consistently, UNC1999, a dual EZH1/2 inhibitor, unlike the EZH2 selective inhibitor EPZ005687, exerts a potent inhibitory effect on MCL cells.Furthermore, we discover CDKN1C and TP53 INP1 as the two important cell cycle regulators, the expression of which are repressed by EZH1/2 mediated epigenetic regulation and are restored by EZH1/2 dual inhibition.Conclusions: Our study suggests that EZH2 participates in the pathogenesis of MCL which may serve as a potential biomarker for prognosis prediction.The dual inhibition of EZH1/2 is a promising therapeutic strategy for MCL. | Wei Li Chengfeng Bi Yating Han Tian Tian Xianhuo Wang Huijing Bao Xiaoying Xu Xuhan Zhang Lu Liu Weiwei Zhang Hai Gao Huaqing Wang Huilai Zhang Bin Meng Xi Wang Kai Fu | 2019 | Cancer Biology & Medicine2019，16，3： | 2 |
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