检索结果-南通市图书馆

cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy

Acta Pharmaceutica Sinica B 2021年第9期11卷 2738-2748页

作者： Kailin Li Jieqiong You Qian Wu Wen Meng Qiaojun He Bo Yang Chengliang Zhu Ji Cao College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Innovation Institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310058China Affiliated Hangzhou First People’s Hospital Zhejiang University School of MedicineHangzhou 310058China Cancer Center of Zhejiang University Hangzhou 310058China

Synthetic lethality is a proven effective antitumor strategy that has attracted great ***-scale screening has revealed many synthetic lethal genetic phenotypes,and relevant smallmolecule drugs have also been implemented in clinical *** evidence suggests that CDKs,constituting a kinase family predominantly involved in cell cycle control,are synthetic lethal factors when combined with certain oncogenes,such as MFC,TP53,and RAS,which facilitate numerous antitumor treatment options based on CDK-related synthetic *** this review,we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.

关键词： Synthetic lethality cyclin-dependent kinase Antitumor therapy Oncogenes MYC P53 RAS PARP

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Long non-coding RNA H19 promotes proliferation inhepatocellular carcinoma cells via H19/miR-107/CDK6 axis

引用

肿瘤学研究(英文) 2023年第6期31卷 989-1005页

作者： ARCHITTAPON NOKKEAW PANNATHON THAMJAMRASSRI NAPHAT CHANTARAVISOOT PISIT TANGKIJVANICH CHAIYABOOT ARIYACHET Department of Biochemistry Faculty of MedicineChulalongkorn UniversityBangkok10330Thailand Center of Excellence in Hepatitis and Liver Cancer Faculty of MedicineChulalongkorn UniversityBangkok10330Thailand Department of Biochemistry Medical Biochemistry ProgramFaculty of MedicineChulalongkorn UniversityBangkok10330Thailand Center of Excellence in Systems Biology Faculty of MedicineChulalongkorn UniversityBangkok10330Thailand

Hepatocellular carcinoma (HCC) is the leading cause of cancer death worldwide;nevertheless, currenttherapeutic options are limited or ineffective for many patients. Therefore, elucidation of molecular mechanisms inHCC biology could yield important insights for the intervention of novel therapies. Recently, various studies havereported dysregulation of long non-coding RNAs (lncRNAs) in the initiation and progression of HCC, including H19;however, the biological function of H19 in HCC remains unclear. Here, we show that knockdown of H19 disruptedHCC cell growth, impaired the G1-to-S phase transition, and promoted apoptosis, while overexpression of H19yielded the opposite results. Screening for expression of cell cycle-related genes revealed a significant downregulationof CDK6 at both RNA and protein levels upon H19 suppression. Bioinformatic analysis of the H19 sequence and the3′ untranslated region (3′ UTR) of CDK6 transcripts showed several binding sites for microRNA-107 (miR-107), andthe dual luciferase reporter assay confirmed their direct interaction with miR-107. Consistently, blockage of miR-107activity alleviated the growth suppression phenotypes induced by H19 downregulation, suggesting that H19 serves asa molecular sponge for miR-107 to promote CDK6 expression and cell cycle progression. Together, this studydemonstrates a mechanistic function of H19 in driving the proliferation of HCC cells and suggests H19 suppressionas a novel approach for HCC treatment.

关键词： HCC H19 Long-noncoding RNA MicroRNA cyclin-dependent kinase CDK6

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Cell cycle regulation and hematologic malignancies

引用

Blood Science 2019年第1期1卷 34-43页

作者： Yun Dai Fengyan Jin Wei Wu Shaji K.Kumar Laboratory of Cancer Precision Medicine The First Hospital of Jilin UniversityChangchunJilinChina Department of Hematology Cancer CenterThe First Hospital of Jilin UniversityChangchunJilinChina Department of Neurosurgery The First Hospital of Jilin UniversityChangchunJilinChina Division of Hematology Mayo ClinicRochesterMNUSA

A complex network precisely regulates the cell cycle through the G1,S,G2,and M phases and is the basis for cell division under physiological and pathological *** the one hand,the transition from one phase to another as well as the progression within each phase is driven by the specific cyclin-dependent kinases(CDKs;e.g.,CDK1,CDK2,CDK4,CDK6,and CDK7),together with their exclusive partner cyclins(e.g.,cyclin A1,B1,D1–3,and E1).On the other hand,these phases are negatively regulated by endogenous CDK inhibitors such as p16^(ink4a),p18^(ink4c),p19^(ink4d),p21^(cip1),and p27^(kip1).In addition,several checkpoints control the commitment of cells to replicate DNA and undergo mitosis,thereby avoiding the passage of genomic errors to daughter *** are often constitutively activated in cancer,which is characterized by the uncontrolled proliferation of transformed cells,due to genetic and epigenetic abnormalities in the genes involved in the cell ***,several oncogenes and defective tumor suppressors promote malignant changes by stimulating cell cycle entry and progression or disrupting DNA damage responses,including the cell cycle checkpoints,DNA repair mechanisms,and ***,genes or proteins related to cell cycle regulation remain the main targets of interest in the treatment of various cancer types,including hematologic *** this context,advances in the understanding of the cell cycle regulatory machinery provide a basis for the development of novel therapeutic *** present article summarizes the pathways as well as their genetic and epigenetic alterations that regulate the cell cycle;moreover,it discusses the various approved or potential therapeutic targets associated with the cell cycle,focusing on hematologic malignancies.

关键词： Cell cycle Transcription cyclin cyclin-dependent kinase Hematologic malignancy

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

A plant viral protein disrupts mitosis and contributes to host dwarfism by directly interrupting the conserved mitotic entry switch Wee1-Cdc25-Cdk1

A plant viral protein disrupts mitosis and contributes to ho...

引用

第十届全国小麦基因组学及分子育种大会

作者： Huaibing Jin Zhiqiang Du Yanjing Zhang Judit Antal Zongliang Xia Yan Wang Yang Gao Xiaoge Zhao Xinyun Han Yanjun Cheng Qianhua Shen Kunpu Zhang Robert E.Elder Zsigmond Benko Csaba Fenyvuesvolgyi Ge Li Dionne Rebello Richard Y.Zhao Daowen Wang State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of Sciences University of Chinese Academy of Sciences College of Agronomy and State Key Laboratory of Wheat and Maize Crop Science Henan Agricultural University Chicago Memorial Institute for Education and Research Northwestern University Feinberg School of Medicine Department of Pathology University of Maryland School of Medicine Department of Microbiology-Immunology Institute of Human Virologyand Institute of Global HealthUniversity of Maryland School of Medicine

Disruption of host mitosis plays an important role in viral pathogenesis However,the underlying molecular mechanisms are still not well ***,we report that the 17 K protein,conserved among the grass-infecting barley yellow dwarf viruses(BYDVs) and related poleroviruses,disrupts G2/M transition and inhibits cell growth in both host(barley) and nonhost(fission yeast and Arabidopsis thaliand)organisms through directly interrupting the mitotic entry switch Weel-Cdc25-Cdkl(CDKA in plant and Cdc2 in fission yeast).17 K binds to Cdc25 and CDKA/Cdc2 but not Weel,and decreases Cdc25’s phosphatase activity in ***,17 K expression up-regulates Weel *** alterations lead to abnormal accumulation of the CDKA/Cdc2 phosphorylated at critical mitosis-regulating residues,which impedes the function of CDKA/Cdc2 and results in G2/M ***,perturbing 17 K-CDKA interaction by silencing CDKA expression aggravates BYDV-induced dwarfing *** work suggests that the 17 K protein is an important contributor to BYDV-induced host *** the interaction between 17 K and Weel-Cdc25-CDKA may aid the control of cereal yellow dwarf ***,direct interruption of Weel-Cdc25-Cdkl is also being found for an increasing number of animal viral proteins,indicating commonality in the molecular mechanism underlying the disruption of mitosis by plant and animal viruses.

关键词： Barley yellow dwarf virus 17K mitosis disruption cyclin-dependent kinase Cdc25 Wee1

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：