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Breast cancer development and progression:Risk factors,cancer stem cells,signaling pathways,genomics,and molecular pathogenesis

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Genes & Diseases 2018年第3期5卷 77-106页

作者： Yixiao Feng Mia Spezia Shifeng Huang Chengfu Yuan Zongyue Zeng linghuan zhang Xiaojuan Ji Wei Liu Bo Huang Wenping Luo Bo Liu Yan Lei Scott Du Akhila Vuppalapati Hue H.Luu Rex C.Haydon Tong-Chuan He Guosheng Ren Chongqing Key Laboratory of Molecular Oncology and Epigenetics Departments of General SurgeryClinical Laboratory MedicineOrthopaedic SurgeryPlastic Surgery and Burnand OtolaryngologyHead and Neck SurgeryThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang 443002China Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing 400016China Stem Cell Biology and Therapy Laboratory Ministry of Education Key Laboratory of Child Development and DisordersThe Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006China Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences The Affiliated Hospital of StomatologyChongqing Medical UniversityChongqing 401147China Student Inquiry Research Program Illinois Mathematics and Science Academy(IMSA)AuroraIL 60506USA

As the most commonly occurring cancer in women worldwide,breast cancer poses a formidable public health challenge on a global *** cancer consists of a group of biologically and molecularly heterogeneous diseases originated from the *** the risk factors associated with this cancer varies with respect to other cancers,genetic predisposition,most notably mutations in BRCA1 or BRCA2 gene,is an important causative factor for this *** cancers can begin in different areas of the breast,such as the ducts,the lobules,or the tissue in *** the large group of diverse breast carcinomas,there are various denoted types of breast cancer based on their invasiveness relative to the primary tumor *** is important to distinguish between the various subtypes because they have different prognoses and treatment *** there are remarkable parallels between normal development and breast cancer progression at the molecular level,it has been postulated that breast cancer may be derived from mammary cancer stem *** breast development and mammary stem cells are regulated by several signaling pathways,such as estrogen receptors(ERs),HER2,and Wnt/b-catenin signaling pathways,which control stem cell proliferation,cell death,cell differentiation,and cell ***,emerging evidence indicates that epigenetic regulations and noncoding RNAs may play important roles in breast cancer development and may contribute to the heterogeneity and metastatic aspects of breast cancer,especially for triple-negative breast *** review provides a comprehensive survey of the molecular,cellular and genetic aspects of breast cancer.

关键词： BRCA1/2 Breast cancer Cancer stem cells Estrogen receptors HER2 Noncoding RNAs Triple-negative breast cancer Tumor heterogeneity

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Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)

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Genes & Diseases 2018年第2期5卷 137-149页

作者： Xinyi Yu Liqun Chen Ke Wu Shujuan Yan Ruyi zhang Chen Zhao Zongyue Zeng Yi Shu Shifeng Huang Jiayan Lei Xiaojuan Ji Chengfu Yuan linghuan zhang Yixiao Feng Wei Liu Bo Huang Bo zhang Wenping Luo Xi Wang Bo Liu Rex C.Haydon Hue H.Luu Tong-Chuan He Hua Gan Departments of Nephrology Orthopaedic SurgeryCardiologyGeneral SurgeryPlastic Surgeryand Clinical Laboratory MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing400016China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang443002China Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330031China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhou730030China

Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of *** the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell *** mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ***,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these *** this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT *** show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP *** imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker *** imPOD cells do not form tumor-like masses in *** further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and ***,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions.

关键词： Chronic kidney disease FLP recombinase Glomerular disease Glomerulus Immortalization Nephropathy Podocyte SV40 T antigen

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Corrigendum to “Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes (imPODs)” [Genes & Diseases 5 (2018) 137–149]

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Genes & Diseases 2023年第2期10卷 630-631页

作者： Xinyi Yu Liqun Chen Ke Wu Shujuan Yan Ruyi zhang Chen Zhao Zongyue Zeng Yi Shu Shifeng Huang Jiayan Lei Xiaojuan Ji Chengfu Yuan linghuan zhang Yixiao Feng Wei Liu Bo Huang Bo zhang Wenping Luo Xi Wang Bo Liu Rex C. Haydon Hue H. Luu Tong-Chuan He Hua Gan Departments of Nephrology Orthopaedic SurgeryCardiologyGeneral SurgeryPlastic Surgeryand Clinical Laboratory MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichangHubei 443002China Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330031China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhouGansu 730030China

The authors regret having an image assembly error in Figure 3A,in which the image for "imPOD Synaptopodin DAPl stain"groupwas erroneouslyduplicatedwiththe imagefrom the"tsPOD-33C SynaptopodinDAPIstain"*** confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and *** authors would like to apologize for any inconvenience caused.

关键词： Cor cytes glomerular

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Transcriptomic landscape regulated by the 14 types of bone morphogenetic proteins(BMPs)in lineage commitment and differentiation of mesenchymal stem cells(MSCs)

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Genes & Diseases 2019年第3期6卷 258-275页

作者： linghuan zhang Qing Luo Yi Shu Zongyue Zeng Bo Huang Yixiao Feng Bo zhang Xi Wang Yan Lei Zhenyu Ye Ling Zhao Daigui Cao Lijuan Yang Xian Chen Bin Liu William Wagstaff Russell R*Reid Hue H*Luu Rex C*Haydon Michael J*Lee Jennifer Moriatis Wolf Zhou Fu Tong-Chuan He Quan Kang Stem Cell Biology and Therapy Laboratory Ministry of Education Key Laboratory of Child Development and DisordersThe Children’s Hospital of Chongqing Medical UniversityChongqing 400014China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA c Ministry of Education Key Laboratory of Diagnostic Medicine School of Laboratory MedicineChicagoIL 60637USA d The Affiliated Hospitals of Chongqing Medical University Chongqing 400016China e Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006China f Key Laboratory of Orthopaedic Surgery of Gansu Province Departments of Orthopaedic Surgery and Obstetrics and GynecologyThe First and Second Hospitals of Lanzhou UniversityLanzhou 730030China g Department of General Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Department of Clinical Laboratory Medicine The Affiliated Hospital of Qingdao UniversityQingdao 266061China Department of Biology School of Life SciencesSouthwest UniversityChongqing 400715China Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Mesenchymal stem cells(MSCs)are ubiquitously-existing multipotent progenitors that can self-renew and differentiate into multiple lineages including osteocytes,chondrocytes,adipocytes,tenocytes and *** represent one of the most commonly-used adult progenitors and serve as excellent progenitor cell models for investigating lineagespecific differentiation regulated by various cellular signaling pathways,such as bone morphogenetic proteins(BMPs).As members of TGFb superfamily,BMPs play diverse and important roles in development and adult *** least 14 BMPs have been identified in *** BMPs exert distinct but overlapping biological *** a comprehensive analysis of 14 BMPs in MSCs,we demonstrated that BMP9 is one of the most potent BMPs in inducing osteogenic differentiation of ***,a global mechanistic view of BMP signaling in regulating the proliferation and differentiation of MSCs remains to be fully ***,we conducted a comprehensive transcriptomic profiling in the MSCs stimulated by 14 types of *** clustering analysis classifies 14 BMPs into three subclusters:an osteo/chondrogenic/adipogenic cluster,a tenogenic cluster,and BMP3 *** also demonstrate that six BMPs(e.g.,BMP2,BMP3,BMP4,BMP7,BMP8,and BMP9)can induce ISmads effectively,while BMP2,BMP3,BMP4,BMP7,and BMP11 up-regulate Smad-independent MAP kinase ***,we show that many BMPs can upregulate the expression of the signal mediators of Wnt,Notch and PI3K/AKT/mTOR *** the reported transcriptomic changes need to be further validated,our expression profiling represents the first-of-its-kind to interrogate a comprehensive transcriptomic landscape regulated by the 14 types of BMPs in MSCs.

关键词： Bone morphogenetic proteins(BMPs) MAP kinase signaling Mesenchymal stem cells Notch signaling PI3K/AKT/mTOR pathway Smad signaling TGFb superfamily Wnt signaling

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Corrigendum to “Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference” [Genes & Diseases 5(2018):172–184]

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Genes & Diseases 2023年第2期10卷 632-637页

作者： Shujuan Yan Ruyi zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong linghuan zhang Wei Liu Yixiao Feng Bo zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu Rex C. Haydon Michael J. Lee Russell R. Reid Jennifer Moriatis Wolf Qiong Shi Hue H. Luu Tong-Chuan He Yaguang Weng Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA The School of Pharmacy and the Affiliated Hospitals of Chongqing Medical University Chongqing 400016China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhouGansu 730030China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichangHubei 443002China Department of Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhanHubei 430071China Department of Orthopaedic Surgery Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangshaHunan 410011China Department of Surgery Laboratory of Craniofacial Biology and DevelopmentSection of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

The authors regret having several image assembly ***,in Figure 3A panel b,the image for "AdsimB9-4 only"group was erroneously duplicated with an overlapping image from the"AdRFp"group;and the image for"AdsimB9-1+BMP9"groupwas erroneouslyduplicatedwithan overlapping image from"AdsimB9-8+BMP9"*** Figure 4Apanel a,the images for"BMP9"group and "BMP9+simB9-4"group were erroneously duplicated with an overlapping image from"simB9-4"*** Figure 5A,the image for"BMP9+simB9-4/Day3"group was erroneously duplicated with an overlapping image from"BMP9+simB9-7/Day3"group;and the image for"BMP9+simB9-4/Day5"group was erroneously duplicated with an overlapping image from an unrelated *** Figure 6B,the image for"BMP9+simB9-7/Day 11"group was erroneously duplicated with an overlapping image from the"BMP9+simB9-4/Day 11"group.

关键词： Figure BMP9 Cor

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Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model

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Science China Life Sciences 2024年

作者： Weiwei zhang linghuan Wang Yujia Wang Yan Fang Ruihua Cao Zhiyi Fang Dong Han Xu Huang Zhenghui Gu Yingjie zhang Yan Zhu Yan Ma Feng Cao Department of Cardiology The Second Medical Centre Chinese PLA General Hospital National Clinical Research Center for Geriatric Diseases School of Medicine Nankai University Department of Cardiology Beijing Friendship Hospital Capital Medical University

Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease （ASCVD）, which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors （SGLT2is） reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE-/-control mice treated with normal saline, those in the ApoE-/-dapagliflozin group, receiving intragastric dapagliflozin （0.1 mg kg-1d-1） for 14 weeks, exhibited the reduction in the total aortic plaque area （48.8%±6.6%vs. 74.6%±8.0%,P<0.05）, the decrease in the lipid core area (（0.019±0.0037） mm2vs.（0.032±0.0062） mm2, P<0.05) and in the percentage of senescent cells within the plaques （16.4%±3.7%vs. 30.7%±2.0%, P<0.01）, while the increase in the thickness of the fibrous cap (（21.6±2.1）μm vs.（14.6±1.5）μm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin’s mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells （HASMCs） was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα *** analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 s

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Corrigendum to “The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs” [Genes & Diseases 5 (2018) 62–74]

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Genes & Diseases 2023年第2期10卷 627-629页

作者： Zongyue Zeng Bo Huang Shifeng Huang Ruyi zhang Shujuan Yan Xinyi Yu Yi Shu Chen Zhao Jiayan Lei Wenwen zhang Chao Yang Ke Wu Ying Wu Liping An Xiaojuan Ji Cheng Gong Chengfu Yuan linghuan zhang Wei Liu Yixiao Feng Bo zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Rex C. Haydon Hue H. Luu Lan Zhou Russell R. Reid Tong-Chuan He Xingye Wu Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang 330006China Departments of Clinical Laboratory Medicine General SurgeryOrthopedic SurgeryNephrologyand CardiologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China The Children's Hospital Chongqing Medical UniversityChongqing 400014China Department of Laboratory Medicine and Clinical Diagnostics The Affiliated Yantai HospitalBinzhou Medical UniversityYantai 264100China Department of Immunology and Microbiology Beijing University of Chinese MedicineBeijing 100029China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhou 730030China Department of Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang 443002China Department of Orthopaedic Surgery Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangsha 410011China Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences Chongqing 401147China The Affiliated Hospital of Stomatology of Chongqing Medical University Chongqing 401147China Department of Surgery Laboratory of Craniofacial Biology and DevelopmentSection of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

The authors regret having an image assembly error in Figure 5Ca,in which the image for the "Oh dBiFP-AdRFp"group was erroneously duplicated with an overlapping image from the"36h BiFP dBIFP-AdR-simH19"*** confirm the error is restricted to the image assembly,and the underlying data and conclusions are correct and *** authors would like to apologize for any inconvenience caused.

关键词： image Figure unchanged

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Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through RNA interference

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Genes & Diseases 2018年第2期5卷 172-184页

作者： Shujuan Yan Ruyi zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong linghuan zhang Wei Liu Yixiao Feng Bo zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu Rex C.Haydon Michael J.Lee Russell R.Reid Jennifer Moriatis Wolf Qiong Shi Hue H.Luu Tong-Chuan He Yaguang Weng Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA The School of Pharmacy and the Affiliated Hospitals of Chongqing Medical University Chongqing 400016China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhou730030China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang 443002China Department of Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Orthopaedic Surgery Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangsha 410011China Department of Surgery Laboratory of Craniofacial Biology and DevelopmentSection of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic *** previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully ***,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of *** two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus *** demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in ***,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from ***,our findings demonstrate the important role of BMP9 in osteogenic differentiation of *** characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic *** results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.

关键词： BMP9 Bone formation Mesenchymal stem cells Osteogenic differentiation RNA interference Recombinant adenovirus siRNA

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The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncRNAs

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Genes & Diseases 2018年第1期5卷 62-74页

作者： Zongyue Zeng Bo Huang Shifeng Huang Ruyi zhang Shujuan Yan Xinyi Yu Yi Shu Chen Zhao Jiayan Lei Wenwen zhang Chao Yang Ke Wu Ying Wu Liping An Xiaojuan Ji Cheng Gong Chengfu Yuan linghuan zhang Wei Liu Yixiao Feng Bo zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Rex C.Haydon Hue H.Luu Lan Zhou Russell R.Reid Tong-Chuan He Xingye Wu Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330006China Departments of Clinical Laboratory Medicine General SurgeryOrthopedic SurgeryNephrologyand CardiologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China The Children’s Hospital Chongqing Medical UniversityChongqing400014China Department of Laboratory Medicine and Clinical Diagnostics The Affiliated Yantai HospitalBinzhou Medical UniversityYantai264100China Department of Immunology and Microbiology Beijing University of Chinese MedicineBeijing100029China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhou730030China Department of Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhan430071China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang443002China Department of Orthopaedic Surgery Chongqing Hospital of Traditional Chinese MedicineChongqing400021China Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangsha410011China Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences Chongqing401147China The Affiliated Hospital of Stomatology of Chongqing Medical University Chongqing401147China Department of Surgery Laboratory of Craniofacial Biology and DevelopmentSection of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL60637USA

While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mRNAs,leaving most of the transcripts as noncoding RNAs,such as microRNAs and long-noncoding RNAs(lncRNAs),which are critical components of epigenetic *** are emerging as critical regulators of gene expression and genomic ***,it remains largely unknown about how lncRNAs are ***,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncRNA transcript levels in a high throughput ***,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP *** further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncRNA H19 chimeric transcript is silenced by mouse H19-specific ***,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncRNAs by microRNAs,synthetic regulatory RNA molecules,RNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders.

关键词： BiFP Green fluorescent protein High throughput screening lncRNA Noncoding RNA Transcript reporter assay

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贵阳地区153例哮喘患儿IL-13G＋2044A和IL-13A-1512C基因多态性研究

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中华微生物学和免疫学杂志 2016年第2期36卷 144-148页

作者：张金凤杨俊李波张龄幻朱晓萍贵州医科大学附属医院儿科贵阳550004

目的探讨白细胞介素13（interleukin-13，IL-13）基因外显子4区G＋2044A和启动子A-1512C的单核苷酸多态性与贵阳地区儿童支气管哮喘的相关关系。方法用SequenomMassArray质谱阵列技术平台定制SNP芯片技术检测153例哮喘组儿童[男性89例... 详细信息

目的探讨白细胞介素13（interleukin-13，IL-13）基因外显子4区G＋2044A和启动子A-1512C的单核苷酸多态性与贵阳地区儿童支气管哮喘的相关关系。方法用SequenomMassArray质谱阵列技术平台定制SNP芯片技术检测153例哮喘组儿童[男性89例，女性64例，平均年龄为（5．68±3．33）岁]和103例对照组儿童[男性65例，女性38例，平均年龄为（4．85±3．69）岁]IL-13G＋2044A和IL-13A-1512C的基因型分布。结果IL-13G＋2044A在哮喘组和对照组儿童中均存在GG、GA、AA三种基因型，此位点的基因型频率分布在两组间的差异具有统计学意义（P〈0，05）。IL-13G＋2044A位点的A变异等位基因携带者患病危险性高于非携带者，差异有统计学意义（P〈0．01）。在哮喘组和对照组IL-13A-1512C均存在3种基因型：AA、AC、CC，两组的基因型和等位基因频率，差异有统计学意义（P〈0．01）。结论IL-13G＋2044A和IL一13A-1512C多态性位点可能与贵阳地区儿童哮喘呈相关关系。IL-13G＋2044A位点的变异等位基因A可能是贵阳地区儿童哮喘的重要易感因素。IL-13A-1512C位点的变异等位基因C可能是贵阳地区哮喘患儿的保护性因素。

关键词：支气管哮喘 IL-13 G+2044A A-1512C 贵阳地区

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