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World Journal of Gastrointestinal Oncology 2016年第3期8卷 282-288页

作者： Yuning Hou Xiaoqing Guan Zhe Yang Chunying Li department of biochemistry and Molecular Biology Karmanos Cancer Institute Wayne State University School of Medicine

Cystic fibrosis transmembrane conductance regulator(CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers.

关键词： Gastrointestinal cancer Protein interaction Cystic fibrosis transmembrane conductance regulator Nuclear factor &kappa B Signaling molecule

P53 rs1042522 and CD95 rs1800682 genetic variations in HCV-4a response to antiviral therapy

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Genes & Diseases 2015年第2期2卷 197-210页

作者： Ahmed A.Abd-Rabou Emad F.Eskander Mervat S.Mohamed Shaymaa M.M.Yahya Ashraf El Sherbini Olfat G.Shaker Hormones department Medical Research DivisionNational Research CentreCairo 12622Egypt Chemistry department Biochemistry SpecialtyFaculty of ScienceCairo UniversityEgypt Internal Medicine department Medical Research DivisionNational Research CentreCairoEgypt Medical biochemistry and Molecular Biology department Faculty of MedicineCairo UniversityEgypt

Current estimates indicate that the hepatitis C(HCV)is the leading cause of mortality around the world,with infection rates steadily increasing in *** dual therapy for this silent epidemic with pegylated-interferon-a2b/ribavirin has markedly improved the success rates in genotype-4 *** was reported that apoptosis plays a vital mechanistic role in limiting viral replication.P53,a key regulator of apoptosis,induces CD95 gene expression and subsequently initiates apoptotic cascade to be *** current study examined the impact of P53 rs1042522 and CD95 rs1800682 polymorphisms on the treatment *** groups of 240 volunteers were enrolled in this study;86 in sustained virological responders group,74 in non-responders group,and 80 in control *** patients had HCV genotype-4a and were interferon treatment naı¨*** of HCV-RNA by qRT-PCR and histological scores were performed for all *** addition,genotyping of HCV-RNA,P53 rs1042522 Arg/Pro and CD95 rs1800682 A/G polymorphisms were investigated in all *** was resulted that P53 Pro/Pro homozygous genotype has high significant increase,while CD95 A/A homozygous genotype has high significant decrease when comparing non-responders with ***,it was concluded that Pro variant of P53 rs1042522 may be used as a genetic predictor for non-responsiveness,while A/A variant of CD95 rs1800682 may be used as a sensitive biomarker for responsiveness to antiviral therapy of HCV genotype-4a *** addition,low prolactin,high total testosterone,and high GH levels may provide promising biomarkers for early prediction of the response when associated with these genetic polymorphisms.

关键词： CD95 rs1800682 HCV gentotype-4a P53 rs1042522 Response SNPs

The heterogeneity of store-operated calcium entry in melanoma

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Science China(Life Sciences) 2016年第8期59卷 764-769页

作者： Robert Hooper M.Raza Zaidi Jonathan Soboloff Fels Institute for cancer research and Molecular Biology Lewis Katz School of Medicine at Temple University department of Medical Genetics & Molecular biochemistry Lewis Katz School of Medicine at Temple University

Calcium is a key regulator of many physiological processes that are perturbed in cancer, such as migration, proliferation and apoptosis. The proteins STIM and Orai mediate store-operated calcium entry(SOCE), the main pathway for calcium entry in non-excitable cells. Changes in the expression and function of STIM and Orai have been found in a range of cancer types and thus implicated in disease progression. Here we discuss the role of STIM, Orai and the SOCE pathway in the progression of melanoma and explore how the heterogeneous nature of melanoma may explain the lack of consensus in the field regarding the role of SOCE in the progression of this disease.

关键词： melanoma STIM1 Orail metastasis

LSD1 coordinates with the SIN3A/HDAC complex and maintains sensitivity to chemotherapy in breast cancer

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Journal of Molecular Cell Biology 2018年第4期10卷 285-301页

作者： Yang Yang Wei Huang Rongfang Qiu Ruiqiong Liu Yi Zeng Jie Gao Yu Zheng Yongqiang Hou Shuang Wang Wenqian Yu Shuai Leng Dandan Feng Yan Wang 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics Tianjin Key Laboratory of Cellular and Molecular Immunology Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Department of Biochemistry and Molecular Biology School of Basic Medical Sciences Tianjin Medical University Tianjin 300070 China department of Biotherapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and Therapy Tianjin Clinical Research Center for Cancer Key Laboratory of Cancer Immunology and Biotherapy Tianjin 300060 China department of biochemistry and Molecular Biology School of Basic Medical Sciences Capital Medical University Beijing 100069 China

Lysine-specific demethylase 1 （LSD1） was the first histone demethylase identified as catalysing the removal of mono- and di-methylation marks on histone H3-K4. Despite the potential broad action of LSD1 in transcription regulation, recent studies indicate that LSD1 may coordinate with multiple epigenetic regulatory complexes including CoREST/HDAC complex, NuRD complex, SIRT1, and PRC2, implying complicated mechanistic actions of this seemingly simple enzyme. Here, we report that LSD1 is also an integral component of the SIN3A/HDAC complex. Transcriptional target analysis using ChIP-on-chip technology revealed that the LSD1/SIN3A/HDAC complex targets several cellular signalling pathways that are critically involved in cell proliferation, survival, metastasis, and apoptosis, especially the p53 signalling pathway. We have demonstrated that LSD1 coordinates with the SIN3A/HDAC complex in inhibiting a series of genes such as CASP7, TGFB2, CDKN1A（p21）, HIF1A, TERT, and MDM2, some of which are oncogenic. Our experiments also found that LSD1 and SIN3A are required for optimal survival and growth of breast cancer cells while also essential for the maintenance of epithelial homoeostasis and chemosensitivity. Our data indicate that LSD1 is a functional alternative subunit of the SIN3A/HDAC complex, providing a molecular basis for the interplay of histone demethylation and deacetylation in chromatin remodelling, and suggest that the LSD1/SIN3A/HDAC complex could be a target for breast cancer therapeutic strategies.

关键词： LSD1 SIN3A breast cancer metastasis chemotherapy sensitivity

Bone marrow microRNA-34a is a good indicator for response to treatment in acute myeloid leukemia

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Oncology research 2024年第3期32卷 577-584页

作者： MONA SA BDELLATEIF NAGLAA MHASSAN MAHMOUD MKAMEL YOMNA MEL-MELIGUI department of cancer Biology Medical Biochemistry and Molecular BiologyNational Cancer InstituteCairo UniversityCairo11976Egypt department of Cinical Pathology National Cancer InstituteCairo UniversityCairo11976Egypt

Background:microRNA 34a(miR 34a)had been reported to have a diagnostic role in acute myeloid leukemia(AML).However,its value in the bone marrow(BM)of AML patients,in addition to its role in response to therapy is still *** current study was designed to assess the diagnostic,prognostic,and predictive significance of miR 34a in the BM of AML ***:The miR.34a was assed in BM aspirate of 82 AML patients in relation to 12 normal control subjects using *** data were assessed for correlation with the relevant dinical critenia,response to therapy,disease-free survival(DFS),and overall survival(OS)***:miR.34a was significantly downregulated in AML patients[0.005(3.3×10^(-6)-1.32)],compared to the control subjects[0.108(3.2× 10^(-4)-1.64),p=0.021].*** relative quantification(RQ)of miR-34a was 0.106(range;0-32.12).The specifaity,sensitivity,and area under the curve(AUC)for the diagnosis of AML were(58.3%,69.5%,0.707,respectively,p=0.021).patients with upregulated miR-34a showed decreased platelets count<34.5 × 10^(9)/L,and achieved early complete remission(CR,p=0.031,p=0.044,respectively).Similarly,patients who were refractory to therapy showed decreased miR 34a levels in comparison to those who achieved CR[0.002(0-0.01)and 0.12(0-32.12),respectively,p=0.002].Therefore,miR 34a could significantly identify patients with CR with a specificity of 75%and sensitivity of 100%at a cut-off of 0.014(AUC=0.927,p=0.005).There was no considerable association between miR-34a expression and survival rates of the induded AML ***:miR-34a could be a beneficial diagnostic biomarker for AML *** addition,it serves as a good indicator for response to therapy,which could possibly identify patients who are refractory to treatment with 100%sensitivity and 75%specificity.

关键词： AML miR 34a microRNA Leukemia

BAT-tling oxidative stress through BCAA catabolism

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Life Metabolism 2024年第5期3卷 42-44页

作者： Maria Delgado-Martin Qiaoqiao Zhang Lawrence Kazak Rosalind&Morris goodman cancer Institute and department of biochemistry McGill UniversityMontrealQCH3A 1A3Canada department of biochemistry McGill UniversityMontrealQCH3G 1Y6Canada

Elevated circulating levels of branched-chain amino acids(BCAAs)are associated with the development of type 2 diabetes and obesity,diseases that can be countered by the energy dissipating(thermogenic)function of brown adipose tissue(BAT).In a recent study published in Cell,Verkerke and colleagues report that BAT promotes insulin sensitivity in the liver by coupling antioxidant homeostasis with BCAA catabolism,an effect that is independent of its thermogenic properties.

关键词： BCAA properties. homeostasis

Conocarpus erectus L., a plant with a high content of structural sugars, ions and phenolic compounds, shows antioxidant and antimicrobial properties promoted by different organic fractions

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Asian Pacific Journal of Tropical Biomedicine 2018年第9期8卷 463-470页

作者： Dayane Kelly Dias do Nascimento Santos Weslley Henrique de Oliveira Melo Anastassia Mariáh Nunes de Oliveira Lima Iranildo Joseda Cruz Filho Glaucia Manoella de Souza Lima Tulio Diego da Silva Maiara Celine de Moura Marcia Silva do Nascimento Ana Maria Souto Maior Thiago Henrique Napoleao Cristiane Moutinho Lagos de Melo department of biochemistry Biosciences Centre Federal University of Pernambuco department of Antibiotics Biosciences Centre Federal University of Pernambuco Center of Strategic Technologies of the Northeast

Objective: To evaluate the structural and chemical composition of plant and the antioxidant and antimicrobial activities promoted by hexanic, ethanolic and ethyl acetate fractions obtained from leaves of Conocarpus ***: Organic fractions were characterized through UPLC-MS and *** potential was performed through DPPH and molybdenum phosphate *** and antifungal assays were performed in accordance with Clinical and Laboratory Standards Institute ***: The obtained biomass of Conocarpus erectus leaves showed the high presence of glucose(0.45 g/L), cellulose(28.69%), Na(55.126 μg/L) and K(31.163 μg/L).We identified seven compounds in the hexanic and ethyl acetate fractions, and eight compounds in ethanolic ***, phenolic compounds are prevalent in all organic fractions with values of(10.04 ± 0.24),(221.26 ± 1.84),(340.53 ± 0.84) mg/g GAE to hexanic, ethyl acetate and ethanolic fraction, *** results showed a high potential in ethyl acetate fraction(71.82 ± 6.87)% and(10.89 ± 0.05)% in DPPH and molybdenum phosphate techniques, *** ethanolic fraction showed moderate bacteriostatic and bactericidal activity against Staphylococcus aureus and presented a high fungistatic potential for all Candida species ***: Organic fractions obtained from leaves of Conocarpus erectus present antimicrobial and antioxidant properties, and these findings contribute to scientific information for the effectiveness on use of this plant in the development of a phytotherapic compound.

关键词： Combretaceae Phenolic compounds Antimicrobial activity Antioxidant

Kinetochore protein MAD1 participates in the DNA damage response through ataxia-telangiectasia mutated kinase-mediated phosphorylation and enhanced interaction with KU80

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cancer Biology & Medicine 2020年第3期17卷 640-651页

作者： Mingming Xiao Xuesong Li Yang Su Zhuang Liu Yamei Han Shuai Wang Qinghua Zeng Hong Liu Jianwei Hao Bo Xu department of biochemistry and Molecular Biology Key Laboratory of Breast Cancer Prevention and TherapyMinistry of EducationTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin's Clinical Research Center for CancerTianjin 300060China department of Oncology Southern Research InstituteBirminghamAL 35205USA department of Neurosurgery Tianjin Huanhu HospitalTianjin 300350China Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases Tianjin 300350China Center for Intelligent Oncology Chongqing University Cancer HospitalChongqing University School of MedicineChongqing 400030China

Objective:Mitotic arrest-deficient protein 1(MAD1)is a kinetochore protein essential for the mitotic spindle *** studies have indicated that MAD1 is a component of the DNA damage response(DDR)***,whether and how MAD1 might be directly involved in the DDR is largely ***:We ectopically expressed the wild type,or a phosphorylation-site--mutated form of MAD1 in MAD1 knockdown cells to look for complementation *** used the comet assay,colony formation assay,immunofluorescence staining,and flow cytometry to assess the DDR,radiosensitivity,and the G2/M *** employed co-immunoprecipitation followed by mass spectrometry to identify MAD1 interacting *** were analyzed using the unpaired Student'***:We showed that MAD1 was required for an optimal DDR,as knocking down MAD1 resulted in impaired DNA repair and hypersensitivity to ionizing radiation(IR).We found that IR-induced serine 214 phosphorylation was ataxia-telangiectasia mutated(ATM)*** of serine 214 to alanine failed to rescue the phenotypes of MAD1 knockdown cells in response to *** mass spectrometry,we identified a protein complex mediated by MAD1 serine 214 phosphorylation in response to *** them,we showed that KU80 was a key protein that displayed enhanced interaction with MAD1 after DNA ***,we showed that MAD1 interaction with KU80 required serine 214 phosphorylation,and it was essential for activation of DNA protein kinases catalytic subunit(DNA-PKcs).Conclusions:MAD1 serine 214 phosphorylation mediated by ATM kinase in response to IR was required for the interaction with KU80 and activation of DNA-PKCs.

关键词： DNA damage response ataxia-telangiectasia mutated kinase(ATM) mitotic arrest-deficient protein 1(MAD1) KU80 protein DNA-PKcs

Functional relationship between p53 and RUNX proteins

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Journal of Molecular Cell Biology 2019年第3期11卷 224-230页

作者： Suk-Chul Bae Arun Mouli Kolinjivadi Yoshiaki Ito department of biochemistry School of Medicineand Institute for Tumour ResearchChungbuk National UniversityCheongju 28644South Korea cancer Science Institute of Singapore National University of SingaporeSingapore 117599Singapore

RUNX genes belong to a three-membered family of transcription factors,which are well established as master regulators of *** them,aberrations in RUNX3 expression are frequently observed in human malignancies primarily due to epigenetic silencing,which is often *** the G1 phase of the cell cycle,RUNX3 regulates the restriction(R)-point,a mechanism that decides cell cycle *** at the R-point or loss of RUNX3 results in premature entry into S phase,leading to a proliferative *** of Runxl and Runx2 induce immortalization of mouse embryo *** a consequence,RUNX loss induces pre-cancerous lesions independent of oncogene activation.p53 is the most extensively studied tumour suppressor.p53 plays an important role to prevent tumour progression but not tumour ***,upon oncogene activation,early inactivation of RUNX genes and subsequent mutation of p53 appear to result in tumour initiation and ***,transcription-independent DNA repairing roles of RUNX3 and p53 are *** evolutionarily old genes,it appears that the primordial function of p53 is to protect genome integrity,a function that likely extends to the RUNX gene as *** this review,we examine the mechanism and sequence of actions of these tumour suppressors in detail.

关键词： RUNX tumour suppressor p53

CARM1 drives triple-negative breast cancer progression by coordinating with HIF1A

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Protein & Cell 2024年第10期15卷 744-765页

作者： Dandan Feng Jie Gao Ruiqiong Liu Wei Liu Tianyang Gao Yunkai Yang Die Zhang Tianshu Yang Xin Yin Hefen Yu Wei Huang Yan Wang Key Laboratory of cancer and Microbiome State Key Laboratory of Molecular OncologyNational Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China department of Clinical Laboratory The Second Hospital of Shandong UniversityJinan 250033China department of cancer Center The Second Hospital of Shandong UniversityJinan 250033China Beijing Key Laboratory of cancer Invasion and Metastasis research Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Coactivator-associated arginine methyltransferase 1(CARM1)promotes the development and metastasis of estro-gen receptor alpha(ERa)-positive breast *** function of CARM1 in triple-negative breast cancer(TNBC)is still unclear and requires further ***,we report that CARM1 promotes proliferation,epithelial-mesen-chymal transition,and stemness in ***1 is upregulated in multiple cancers and its expression correlates with breast cancer ***-wide analysis of CARM1 showed that CARM1 is recruited by hypoxia-inducible factor-1 subunit alpha(HIF1A)and occupy the promoters of CDK4,Cyclin D1,β-Catenin,HIF1A,MALAT1,and SIX1 critically involved in cell cycle,HIF-1 signaling pathway,Wnt signaling pathway,VEGF signaling pathway,thereby modulating the proliferation and invasion of TNBC *** demonstrated that CARM1 is physically associated with and directly interacts with ***,we found that ellagic acid,an inhibitor of CARM1,can suppress the proliferation and invasion of TNBC by directly inhibiting CDK4 *** research has determined the molecular basis of CARM1 carcinogenesis in TNBC and its effective natural inhibitor,which may provide new ideas and drugs for cancer therapy.

关键词： CARM1 HIF1A CDK4 ellagic acid TNBC