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Chromosome instability functions as a potential therapeutic reference by enhancing chemosensitivity to BCL-XL inhibitors in colorectal carcinoma

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中国药理学报（英文版） 2024年第11期45卷 2420-2431页

作者： Xiao Fang Wen-ying Yu Chun-miao Zhu Nan Zhao Wei Zhao Ting-ting Xie Li-jie Wei Xi-ran Sun Juan Xie Ya Zhao Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Clinical Medical College Yangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research Yangzhou 225001China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research Yangzhou 225001China

Chromosome instability(CIN)and subsequent aneuploidy are prevalent in various human malignancies,influencing tumor progression such as metastases and *** studies demonstrate the development of chemoresistance in high-CIN tumors,which poses significant therapeutic *** the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma(CRC),here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC *** using machine learning methods,we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in *** analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these *** further revealed the critical role of BCL-XL in the viability of high-CIN CRC *** addition,to ease the evaluation of CIN levels in clinic,we developed a three-gene signature as a CIN surrogate to predict prognosis,chemotherapeutic and immune responses in CRC *** results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells,therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

关键词： colorectal carcinoma chromosome instability chemosensitivity BCL-XL Navitoclax WEHI-539

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The regulatory role of ZFAS1/mirnas/mrnas axis in cancer:a systematic review

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Oncology Research 2025年第3期33卷 591-604页

作者： RAHUL KUMAR SINGH SUROJIT MANDAL ADRIJA MOHANTA RITU YADAV RAJIV RANJAN KUMAR RINKU KHATKAR VIVEK UTTAM UTTAM SHARMA MANJIT KAUR RANA MANJU JAIN HARDEEP SINGH TULI AKLANK JAIN Non-Coding RNA and Cancer Biology Laboratory Department of ZoologyCentral University of PunjabGhuddaBathinda151401India Department of Pathology/Lab Medicine All India Institute of Medical SciencesBathinda151001India Department of Biochemistry Central University of PunjabGhuddaBathinda151401India Department of Biotechnology Maharishi Markandeshwar(Deemed to be University)MullanaAmbala133207India

Objectives:Recently,we and others have demonstrated the involvement of Zinc Finger Antisense 1(ZFAS1)in cancer ***,the intricate interplay of ZFAS1 with mirnas and mrnas remains to be fully *** and methods:We followed PRISMA guidelines to retrieve and assess the available literature on the topic“ZFAS1/mirna/mrna axis”and“Cancer”from databases such as PubMed,Google Scholar,and *** also used bioinformatic webtools for analyzing the potential mirna targets of ZFAS1 and its role in survival of cancer patients along with their role in various biological functions and ***:Our literature search and bioinformatic analysis reveals that ZFAS1 serves as a sponge for numerous *** the various targeted mirnas,miR-150-5p stands out as significantly correlated with ZFAS1 across multiple databases(p-value=3.27e-16,R-value=-0.346).Additionally,our Kaplan-Meier survival analysis indicates a noteworthy association between ZFAS1 expression levels and overall poor prognosis and survival rates in ovarian,sarcoma,and pancreatic *** also underscore the involvement of various signaling pathways,including Signal Transducer and Activator of Transcription 3(STAT3),Spindle and Kinetochore-associated Protein 1(SKA1),Lysophosphatidic acid receptor 1(LPAR1),and Wntβ-catenin,in cancer development through the ZFAS1/mirnas/mrnas ***,we identify ZFAS1’s pivotal roles in diverse molecular processes,such as rna binding and ribonucleoprotein ***:In conclusion,this review comprehensively summarizes the latest advancements in understanding the regulatory relationships among ZFAS1,mirnas,and mrnas,emphasizing their collective role in cancer development to propose innovative avenues for cancer *** believe that the intricate relationship among the ZFAS1-mirna-mrna axis may yield potential therapeutic targets for effective cancer management.

关键词： Lncrna mirna mrnas Zinc finger antisense 1(ZFAS1) Cancer biomarker

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Ultrafast Photoinduced Electron Transfer in a Photosensitizer Protein

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CCS Chemistry 2022年第4期4卷 1217-1223页

作者： Dandan Zheng Min Tao Longjiang Yu Xiaohong Liu Andong Xia Jiangyun Wang Laboratory of Non-Coding RNA Institute of BiophysicsChinese Academy of SciencesChaoyang DistrictBeijing 100101 Institute of Chemistry Chinese Academy of SciencesBeijing 100190 Institute of Botany Institution Chinese Academy of SciencesBeijing 100093

Photosystem Ⅱ(PSⅡ)is a large membrane protein(∼700 kDa)complex,harboring P680+,the strongest oxidant known in biological systems,which is responsible for driving tyrosine oxidation and ultimately O_(2) *** the enhancement and expansion of PSⅡ functions through genetic engineering would be beneficial for driving challenging chemical reactions,this has proven difficult due to its enormous ***,we report a genetically encoded,27 kDa photosensitizer protein(PSP3)that recapitulates the initial photoinduced key properties of PSⅡ.Through the genetic incorporation of benzophenone-alanine(BpA)into a fluorescent protein coupled with femtosecond transient absorption measurement,we show that photoinduced electron transfer from residue Tyr203 to the PSP3 chromophore occurs very rapidly(∼1 ps),which is comparable with that of the first electron transfer step in *** PSP3 can be overexpressed in high yield in Escherichia coli and genetically engineered easily,it might facilitate challenging oxidation and reduction reactions in vitro and in vivo.

关键词： photosystemⅡ photoinduced electron transfer photosensitizer protein femtosecond transient absorption strong oxidant strong reductant

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Unlocking epigenetics for precision treatment of Ewing’s sarcoma

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Chinese Journal of Cancer Research 2024年第3期36卷 322-340页

作者： Zhehao Fan Shuangshuang Dong Ning Wang Muhammad Babar Khawar Jingcheng Wang Haibo Sun Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225001China Jiangsu Key Laboratory of Experimental&Translational Non-Coding RNA Research Yangzhou 225001China Department of Pathology Northern Jiangsu People’s Hospital Affiliated to Yangzhou University/Clinical Medical CollegeYangzhou UniversityYangzhou 225001China Department of Orthopedics Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhou 225001China

Ewing’s sarcoma(EWS)is a highly aggressive malignant bone tumor primarily affecting adolescents and young *** the efficacy of chemoradiotherapy in some cases,the cure rate for patients with metastatic and recurrent disease remains ***,there is an urgent need for innovative therapeutic approaches to address the challenges associated with EWS *** regulation,a crucial factor in physiological processes,plays a significant role in controlling cell proliferation,maintaining gene integrity,and regulating *** studies highlight the importance of abnormal epigenetic regulation in the initiation and progression of EWS.A comprehensive understanding of the intricate interactions between EWS and aberrant epigenetic regulation is essential for advancing clinical drug *** review aims to provide a comprehensive overview of both epigenetic targets implicated in EWS,integrating various therapeutic modalities to offer innovative perspectives for the clinical diagnosis and treatment of EWS.

关键词： Ewing’s sarcoma epigenetic targets drug resistance drug development

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Rosaceae phylogenomic studies provide insights into the evolution of new genes

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Horticultural Plant Journal 2025年第1期11卷 389-405页

作者： Lan Jiang Xiaoxu Li Kun Lyu Han Wang Zhiyuan Li Wang Qi Lin Zhang Yunpeng Cao Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation(Wannan Medical College) Central LaboratoryYijishan Hospital of Wannan Medical CollegeWuhuAnhui 241000China Beijing Life Science Academy Beijing 102209China CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture Wuhan Botanical GardenChinese Academy of SciencesWuhanHubei 430074China Center of Economic Botany Core Botanical GardensChinese Academy of SciencesWuhanHubei 430074China Key Laboratory for Tobacco Gene Resources Tobacco Research InstituteChinese Academy of Agricultural SciencesQingdaoShangdong 266000China school of Life Sciences Anhui Agricultural UniversityHefeiAnhui 230036China School of Basic Medical Sciences Hubei University of Chinese MedicineWuhanHubei 430065China

Rosa banksiae,known as Lady Banks'rose,is a perennial ornamental crop and a versatile herb in traditional Chinese *** the lack of genomic resources,we assembled a Hi Fi and Nanopore sequencing-derived 458.58 Mb gap-free telomere-to-telomere high-quality *** genome with a scaffold N50=63.90 *** genome of *** exhibited no lineage-specific whole-genome duplication compared with other *** phylogenomic analysis of 13 Rosaceae and Arabidopsis through a comparative genomics study showed that numerous gene families were lineage-specific both before and after the diversification of *** of these genes are candidates for new genes that have evolved from parental genes through fusion *** genes are divided into three types:Type-I and Type-II genes contain two parental genes that are generated by duplication,distributed in the same and different regions of the genome,respectively;and Type-III can only be detected in one parental ***,Type-I genes are found to have more relaxed selection pressure and lower Ks values than Type-II,indicating that these newly evolved Type-I genes may play important roles in driving phenotypic *** analysis exhibited that newly formed fusion genes can regulate the phenotype traits of plant growth and development,suggesting the functional significance of these *** study identifies new fusion genes that could be responsible for phenotype evolution and provides information on the evolutionary history of recently diverged species in the Rosa *** data represents the major progress in understanding the new fusion genes evolution pattern of Rosaceae and provides an invaluable resource for phylogenomic studies in plants.

关键词： Rosa banksiae Gap-free genome Rosaceae Phenotype Evolutionary patterns

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Potential treatment with Chinese and Western medicine targeting NSP14 of SARS-CoV-2

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Journal of Pharmaceutical Analysis 2021年第3期11卷 272-277页

作者： Chao Liu Xiaoxiao Zhu Yiyao Lu Xianqin Zhang Xu Jia Tai Yang Non-coding RNA and Drug Discovery Key Laboratory of Sichuan Province Chengdu Medical CollegeChengduSichuan610500China Basic Medical School Chengdu Medical CollegeChengduSichuan610500China School of Pharmacy Chengdu Medical CollegeChengduSichuan610500China

The outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a serious global health *** raises an urgent need for the development of effective drugs against the deadly ***-CoV-2 non-structural protein 14(NSP14)carrying rna cap guanine N7-methyltransferase and 30-50 exoribonuclease activities could be a potential drug target for ***14 of SARS-CoV-2 shares 98.7%of similarity with the one(PDB 5NFY)of acute respiratory syndrome(SARS)by ***,the SARS-CoV-2 NSP14 structures were modelled by Modeller 9.18 using SARS NSP14(PDB 5NFY)as template for virtual *** on the docking score from AutoDock Vina1.1.2,18 small molecule drugs were selected for further *** on the 5 ns MD simulation trajectory,binding free energy(DG)was calculated by MM/GBSA *** calculated binding free energies of Saquinavir,Hypericin,Baicalein and Bromocriptine for the N-terminus of the homology model wereà37.2711±3.2160,à30.1746±3.1914,à23.8953±4.4800,andà34.1350±4.3683 kcal/mol,respectively,while the calculated binding free energies wereà60.2757±4.7708,à30.9955±2.9975,à46.3099±3.5689,andà59.8104±3.5389 kcal/mol,respectively,when binding to the ***,the compounds including Saquinavir,Hypericin,Baicalein and Bromocriptine could bind to the N-terminus and C-terminus of the homology model of the SARS-CoV-2 NSP14,providing a candidate drug against SARS-CoV-2 for further study.

关键词： SARS-CoV-2 nonstructural protein 14(NSP14) ZINC database Drug docking

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Mini-organs with big impact:Organoids in liver cancer studies

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Oncology Research 2023年第5期31卷 677-688页

作者： MUHAMMAD BABAR KHAWAR YAJUN WANG ANEEQA MAJEED ALI AFZAL KABEER HANEEF HAIBO SUN Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhouChina Jiangsu Key Laboratory of Experimental and Translational Non-Coding RNA Research YangzhouChina Applied Molecular Biology and Biomedicine Lab Department of ZoologyUniversity of NarowalNarowalPakistan Department of Oncology Haian Hospital of Traditional Chinese MedicineHaianChina Molecular Medicine and Cancer Therapeutics Lab Department of ZoologyFaculty of Sciences TechnologyUniversity of Central PunjabLahorePakistan Chinese Institute for Brain Research(CIBR) BeijingChina

Hepatocellular carcinoma,the most common primary liver cancer and a leading cause of death,is a difficult disease to treat due to its heterogeneous *** models,such as 2D culture and patient-derived xenografts,have not proven ***,the development of 3D culture techniques,such as organoids,which can mimic the tumor microenvironment(TME)and preserve heterogeneity and pathophysiological properties of tumor cells,offers new opportunities for treatment and *** also have the potential for biomarker detection and personalized medication,as well as genome editing using CRISPR/Cas9 to study the behavior of certain genes and therapeutic *** review explores to-the-date development of organoids with a focus on TME modeling in 3D organoid ***,it discusses gene editing using CRISPR/Cas9 in organoids,the challenges faced,and the prospects in the field of organoids.

关键词： Heterogeneity Tumor Organoid Liver Treatment Therapy

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Carnitine palmitoyltransferase 1C promotes EMT-associated cisplatin resistance in non-small cell lung cancer cells

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Cancer Biology & Medicine 2025年第1期22卷 48-66页

作者： Renjie Chen Jiahui Wang Shuoyu Huang Xuefeng Hu Xinran He Tiange Zhang Yunhan Hu Huijun Wei Sihui Nian Yushu Huang Zhihao Wu Research Laboratory of Tumor Microenvironment Wannan Medical CollegeWuhu 241001China School of Laboratory Medicine Wannan Medical CollegeWuhu 241001China School of Anesthesiology Wannan Medical CollegeWuhu 241001China School of Medical Imageology Wannan Medical CollegeWuhu 241001China School of Clinical Medicine Wannan Medical CollegeWuhu 241001China Anhui Province Key Laboratory of Active Biological Macro-molecules Research Wannan Medical CollegeWuhu 241001China Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui Wannan Medical CollegeWuhu 241001China School of Pharmacy Wannan Medical CollegeWuhu 241001China Anhui Province Key Laboratory of Non-coding RNA Basic and Clinical Transformation Wannan Medical CollegeWuhu 241001China Anhui Provincial Engineering Research Center for Dental Materials and Application Wannan Medical CollegeWuhu 241001China

Objective:Lung cancer is the most common cause of cancer-related deaths ***-based chemotherapy is one of the main treatment options for patients with non-small cell lung cancer(NSCLC)but the effectiveness of chemotherapy is encumbered by drug ***,understanding the molecular mechanisms underlying chemotherapy resistance is crucial in improving treatment outcomes and ***:The cell viability assay and apoptosis were used to analyze *** blot analysis and wound healing testing were used to evaluate the epithelial-to-mesenchymal transition(EMT).Immunoprecipitation was used for analysis of protein *** activity was determined using the luciferase reporter *** staining was used to determine reactive oxygen species *** expression patterns of EMT markers and carnitine palmitoyltransferase 1C(CPT1C)were determined by Western blot ***:CPT1C,which was shown to be highly expressed in lung cancer,is associated with cisplatin resistance in NSCLC ***1C depletion increased NSCLC cell sensitivity to cisplatin,while overexpression of CPT1C increased NSCLC cell resistance to *** of EMT mediated CPT1C-induced cisplatin *** expression of Snail reversed the increase in cisplatin sensitivity triggered by CPT1C ***,CPT1C was shown to be regulated at the post-translational level and an E3-ubiquitin ligase,NEDD4L,was shown to be a major regulator of CPT1C stability and ***:These data provide evidence for the first time that the lipid metabolism enzyme,CPT1C,mediates resistance to ***,the use of combination therapy with a CPT1C inhibitor may be a promising new avenue in lung cancer treatment.

关键词： CPT1C chemoresistance EMT NEDD4L NSCLC

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Prognostic SLC family genes promote cell proliferation,migration,and invasion in hepatocellular carcinoma

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生物化学与生物物理学报（英文版） 2021年第8期53卷 1065-1075页

作者： Xiao Fang Ying Liu Wangwen Xiao Nan Zhao Chunmiao Zhu Duonan yu Ya Zhao Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Clinical Medical College Yangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Key Laboratory of Experimental and Translational Non-coding RNA Research Medical CollegeYangzhou UniversityYangzhou 225009China Institute of Translational Medicine Medical CollegeYangzhou UniversityYangzhou 225009China Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Disease and Zoonosis Medical CollegeYangzhou UniversityYangzhou 225009China

The solute carrier (SLC) superfamily genes encode more than 300 members that are responsible for the transmembrane transportation of many essential endogenous and exogenous compounds ranging from nutrients to *** are highly expressed in metabolic organs such as the liver,regulating the homeostasis of metabolites and the disposition of *** contrast to their well-studied roles in physiological and pharmacological processes,little is known about the relationship between SLCs and cancer ***,we aimed to explore the potential role of SLCs in progression and prognosis of hepatocellular carcinoma (HCC),one of the most commonly diag-nosed cancers and leading causes of death *** performing bioinformatics analyses of HCC dataset from The Cancer Genome Atlas database,we identified three novel signature SLCs(SLC51B,SLC22A15,and SLC2A1) that are indicative of poor *** functional analyses suggested the potential regulation of the three prognostic SLCs on cell proliferation and *** knockdown experiments performed in HCC cell lines showed that all three prognostic SLCs positively regulated the proliferation of HCC cells,among which SLC22A 15 and SLC2A 1 were required for migration and invasion of the cells,demonstrating remarkable consistency with the roles identified by bioinformatics methods in ***,our study provides a novel prognos-tic biomarker for HCC and reveals the significant roles of SLCs in HCC progression,which might have been undervalued in the past.

关键词： hepatocellular carcinoma prognostic signature SLC family genes proliferation metastasis

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Inhibition of KDM6B prevents osteoarthritis by blocking growth plate-like H3K27me3 loss in bivalent genes

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Science China Life Sciences 2025年第5期68卷 1423-1436页

作者： Hao Du Yao Zhang Xi Yu Xuanhe You Diwei Wu Ze Du Yongrui Cai Zhenyu Luo Hanpeng Lu Zhixin Liao Bi-Sen Ding Ya Zhao Yan Wang Ke Xiao Fan Yang Fangji Gan Ning Ning Jiancheng Zeng Peiliang Shi Zongke Zhou Shishu Huang Department of Orthopedic Surgery and Orthopedic Research Institute West China HospitalSichuan University Rehabilitation Medicine Center West China HospitalSichuan University Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan University Institute of Translational Medicine Medical CollegeYangzhou University Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research College of Animal Science and Technology Sichuan Agricultural University Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province Sichuan Agricultural University Department of Lower Limb Surgery of Sichuan Province Orthopedic Hospital Central Laboratory of Sichuan Province Orthopedic Hospital Brain Cognition and Brain Disease Institute (BCBDI) Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences (CAS)Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions School of Mechanical Engineering Sichuan University Gem Pharmatech (Chengdu) Co. Ltd.

Osteoarthritis(OA) is the most prevalent joint disorder occurring with articular cartilage degradation. It includes a switch from an articular to a growth plate chondrocyte phenotype. Here, we investigated the histone modification profiles and found significant H3K27me3 loss in OA, which led to disease-associated gene expression. Surprisingly, these genes were occupied by both H3K27me3 and H3K4me3 in normal chondrocytes, showing a poised bivalent state. Furthermore, we observed the derepression of similar bivalent genes in growth plate chondrocytes. Finally, a KDM6B inhibitor GSK-J4 prevented the H3K27me3 loss and cartilage damage in the rat OA model. Our results reveal an inherited bivalent epigenetic signature on developmental genes that makes articular chondrocytes prone to hypertrophy and contributes to a promising epigenetic therapy for OA.

关键词： osteoarthritis histone modifications H3K27me3 bivalency growth plate

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