21 results on '"Yakun Luo"'
Search Results
2. The scaffold protein menin is essential for activating the MYC locus and MYC‐mediated androgen receptor transcription in androgen receptor‐dependent prostate cancer cells
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Yakun Luo, Virginie Vlaeminck‐Guillem, Romain Teinturier, Razan Abou Ziki, Philippe Bertolino, Muriel Le Romancer, and Chang Xian Zhang
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2021
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Catalog
3. MEN1 silencing aggravates tumorigenic potential of AR-independent prostate cancer cells through nuclear translocation and activation of JunD and β-catenin
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Yakun Luo, Virginie Vlaeminck-Guillem, Silvère Baron, Sarah Dallel, Chang Xian Zhang, and Muriel Le Romancer
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Prostate cancer ,AR-independent cells ,MEN1 ,JunD ,β-Catenin ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Recent studies highlighted the increased frequency of AR-low or -negative prostate cancers (PCas) and the importance of AR-independent mechanisms in driving metastatic castration-resistant PCa (mCRPC) development and progression. Several previous studies have highlighted the involvement of the MEN1 gene in PCa. In the current study, we focused on its role specifically in AR-independent PCa cells. Methods Cell tumorigenic features were evaluated by proliferation assay, foci formation, colony formation in soft agar, wound healing assay and xenograft experiments in mice. Quantitative RT-PCR, Western blot and immunostaining were performed to determine the expression of different factors in human PCa lines. Different ChIP-qPCR-based assays were carried out to dissect the action of JunD and β-catenin. Results We found that MEN1 silencing in AR-independent cell lines, DU145 and PC3, resulted in an increase in anchorage independence and cell migration, accompanied by sustained MYC expression. By searching for factors known to positively regulate MYC expression and play a relevant role in PCa development and progression, we uncovered that MEN1-KD triggered the nuclear translocation of JunD and β-catenin. ChIP and 3C analyses further demonstrated that MEN1-KD led to, on the one hand, augmented binding of JunD to the MYC 5′ enhancer and increased formation of loop structure, and on the other hand, increased binding of β-catenin to the MYC promoter. Moreover, the expression of several molecular markers of EMT, including E-cadherin, BMI1, Twist1 and HIF-1α, was altered in MEN1-KD DU145 and PC3 cells. In addition, analyses using cultured cells and PC3-GFP xenografts in mice demonstrated that JunD and β-catenin are necessary for the altered tumorigenic potential triggered by MEN1 inactivation in AR-independent PCa cells. Finally, we observed a significant negative clinical correlation between MEN1 and CTNNB1 mRNA expression in primary PCa and mCRPC datasets. Conclusions Our current work highlights an unrecognized oncosuppressive role for menin specifically in AR-independent PCa cells, through the activation of JunD and β-catenin pathways. more...
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- 2021
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4. Menin–MLL1 Interaction Small Molecule Inhibitors: A Potential Therapeutic Strategy for Leukemia and Cancers
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Qing Shi, Meiqi Xu, Zhijian Kang, Manjie Zhang, and Yakun Luo
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molecule inhibitor ,menin-MLL1 complex ,leukemia ,cancer ,therapeutics strategies ,Organic chemistry ,QD241-441 - Abstract
Encoded by the MEN1 gene, menin protein is a fusion protein that is essential for the oncogenic transformation of mixed-lineage leukemia (MLL) and leads to acute leukemia (AL). Therefore, accumulating evidence has demonstrated that inhibition of the high-affinity relationship between menin and mixed-lineage leukemia 1 (MLL1 and KMT2A) is an effective treatment for MLL-rearranged (MLL-r) leukemia in vitro and in vivo. Meanwhile, recent studies found that menin–MLL1 interaction inhibitors exhibited a firm tumor suppressive ability in specific cancer cells, such as prostate cancer, breast cancer, liver cancer, and lung cancer. Overall, it seems to serve as a novel therapeutic means for cancers. Herein, we review the recent progress in exploring the inhibitors of small molecule menin–MLL1 interactions. The molecular mechanisms of these inhibitors’ functions and their application prospects in the treatment of AL and cancers are explored. more...
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- 2023
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5. Spotlight on porphyrins: Classifications, mechanisms and medical applications
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Fuyu Yang, Meiqi Xu, Xiaoyu Chen, and Yakun Luo
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Pharmacology ,General Medicine - Published
- 2023
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6. MEN1 silencing triggers the dysregulation of mTORC1 and MYC pathways in ER+ breast cancer cells
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Razan Abou Ziki, Romain Teinturier, Yakun Luo, Catherine Cerutti, Jean-Marc Vanacker, Coralie Poulard, Thomas Bachelot, Mona Diab-Assaf, Isabelle Treilleux, Chang Xian Zhang, Muriel Le Romancer, Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL) more...
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Cancer Research ,Endocrinology, Diabetes and Metabolism ,[SDV]Life Sciences [q-bio] ,Breast Neoplasms ,Estrogens ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Oncogenes ,Mechanistic Target of Rapamycin Complex 1 ,Endocrinology ,Oncology ,Proto-Oncogene Proteins ,MCF-7 Cells ,Humans ,Female ,Gene Silencing - Abstract
Menin, encoded by the MEN1 gene, has been identified as a critical factor regulating ESR1 transcription, playing an oncogenic role in ER+ breast cancer (BC) cells. Here, we further dissected the consequences of menin inactivation in ER+ BC cells by focusing on factors within two major pathways involved in BC, mTOR and MYC. MEN1 silencing in MCF7 and T-47D resulted in an increase in phosphor-p70S6K1, phosphor-p85S6K1 and phosphor-4EBP1 expression. The use of an AKT inhibitor inhibited the activation of S6K1 and S6RP triggered by MEN1 knockdown (KD). Moreover, MEN1 silencing in ER+ BC cells led to increased formation of the eIF4E and 4G complex. Clinical studies showed that patients with menin-low breast cancer receiving tamoxifen plus everolimus displayed a trend toward better overall survival. Importantly, MEN1 KD in MCF7 and T-47D cells led to reduced MYC expression. ChIP analysis demonstrated that menin bound not only to the MYC promoter but also to its 5’ enhancer. Furthermore, E2-treated MEN1 KD MCF7 cells displayed a decrease in MYC activation, suggesting its role in estrogen-mediated MYC transcription. Finally, expression data mining in tumors revealed a correlation between the expression of MEN1 mRNA and that of several mTORC1 components and targets and a significant inverse correlation between MEN1 and two MYC inhibitory factors, MYCBP2 and MYCT1, in ER+ BC. The current work thus highlights altered mTORC1 and MYC pathways after menin inactivation in ER+ BC cells, providing insight into the crosstalk between menin, mTORC1 and MYC in ER+ BC. more...
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- 2022
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7. Involvement of the MEN1 Gene in Hormone-Related Cancers: Clues from Molecular Studies, Mouse Models, and Patient Investigations
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Razan Abou Ziki, Yakun Luo, Chang Xian Zhang, Muriel Le Romancer, and Virginie Vlaeminck-Guillem
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0301 basic medicine ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,endocrine system diseases ,business.industry ,Estrogen receptor ,General Medicine ,medicine.disease ,Androgen receptor ,03 medical and health sciences ,Prostate cancer ,030104 developmental biology ,0302 clinical medicine ,Breast cancer ,030220 oncology & carcinogenesis ,medicine ,Cancer research ,Endocrine system ,MEN1 ,business ,Multiple endocrine neoplasia ,Estrogen receptor alpha - Abstract
MEN1 mutation predisposes patients to multiple endocrine neoplasia type 1 (MEN1), a genetic syndrome associated with the predominant co-occurrence of endocrine tumors. Intriguingly, recent evidence has suggested that MEN1 could also be involved in the development of breast and prostate cancers, two major hormone-related cancers. The first clues as to its possible role arose from the identification of the physical and functional interactions between the menin protein, encoded by MEN1, and estrogen receptor α and androgen receptor. In parallel, our team observed that aged heterozygous Men1 mutant mice developed cancerous lesions in mammary glands of female and in the prostate of male mutant mice at low frequencies, in addition to endocrine tumors. Finally, observations made both in MEN1 patients and in sporadic breast and prostate cancers further confirmed the role played by menin in these two cancers. In this review, we present the currently available data concerning the complex and multifaceted involvement of MEN1 in these two types of hormone-dependent cancers. more...
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- 2020
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8. Gut Microbiome and Metabolome Response of Pu-erh Tea on Metabolism Disorder Induced by Chronic Alcohol Consumption
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Liang Zeng, Kang Sun, Liyong Luo, Yan Liu, Yakun Luo, and Xinghua Wang
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Male ,0106 biological sciences ,Alcohol Drinking ,Pharmacology ,medicine.disease_cause ,01 natural sciences ,Camellia sinensis ,Mice ,Metabolomics ,medicine ,Metabolome ,Animals ,Humans ,Bacteria ,Tea ,Chemistry ,010401 analytical chemistry ,Lipid metabolism ,General Chemistry ,Metabolism ,medicine.disease ,Sphingolipid ,Gastrointestinal Microbiome ,0104 chemical sciences ,Metabolism disorder ,Mice, Inbred C57BL ,Alcohols ,General Agricultural and Biological Sciences ,Dysbiosis ,Oxidative stress ,010606 plant biology & botany - Abstract
This study investigated the protective effects of pu-erh tea extract (PTE) on alcohol-induced microbiomic and metabolomic disorders. In chronic alcohol-exposed mice, PTE ameliorated chronic alcoholic consumption-induced oxidative stress, inflammation, lipid accumulation, and liver and colon damage through modulating microbiomic and metabolomic responses. PTE restored the alcohol-induced fecal microbiota dysbiosis by elevating the relative abundance of potentially beneficial bacteria, for example, Bifidobacterium and Allobaculum, and decreasing the relative abundance of potentially harmful bacteria, for example, Helicobacter and Bacteroides. The alcohol-induced metabolomic disorder was modulated by PTE, which was characterized by regulations of lipid metabolism (sphingolipid, glycerophospholipid, and linoleic acid metabolism), amino acid metabolism (phenylalanine and tryptophan metabolism), and purine metabolism. Besides, the bacterial metabolites of phytochemicals in PTE might contribute to the protective effects of PTE. Overall, PTE could be a functional beverage to treat chronic alcohol consumption-induced microbiomic and metabolomic disorders. more...
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- 2020
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9. Pancreatic cancer stem cells expand tumor burden and educate tumor adjacent normal acinar cells to initiate carcinogenesis dependent of the KRAS/CD106/NF-κB positive feedback loop.
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ZhiChong Wu, FanLu LI, YaJie ZHAO, Xue WANG, XiaoMei TANG, HaiMin XU, YaKun LUO, XiaXing DENG, ChengHong PENG, Hennino, Ana, and BaiYong SHEN
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- 2024
10. Generation and characterization of Men1 mutant mouse models for studying MEN1 disease
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Razan Abou Ziki, Chang X. Zhang, and Yakun Luo
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congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,Hepatology ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Mutant ,Enteroendocrine cell ,Disease ,Computational biology ,RC799-869 ,Biology ,Diseases of the digestive system. Gastroenterology ,medicine.disease ,Endocrinology ,medicine ,Identification (biology) ,MEN1 ,Multiple endocrine neoplasia ,Gene - Abstract
Patients with multiple endocrine neoplasia type 1 (MEN1) mutations are predisposed to MEN1 syndrome affecting various endocrine cell lineages. Following its identification in the late 1990s, laboratories around the world, including our own, used gene-targeting approaches in murine models to study the MEN1 gene and its related diseases. Subsequently, this field of research witnessed an upsurge in the use of Men1 mutant mouse models to dissect MEN1 functions. These studies led to unraveling the natural history of MEN disease, and highlighted cellular and molecular mechanisms underlying the development of the disease. In this review, we present the currently available data concerning the generation and characterization of Men1 mutant mouse models in connection with MEN1 syndrome. Key words: Mouse models; The MEN1 gene; Tumorigenesis more...
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- 2019
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11. MEN1 silencing aggravates tumorigenic potential of AR-independent prostate cancer cells through nuclear translocation and activation of JunD and β-catenin
- Author
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Muriel Le Romancer, Silvère Baron, Virginie Vlaeminck-Guillem, Yakun Luo, Chang Xian Zhang, Sarah Dallel, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de Biologie et de Pathologie Sud [HCL, Lyon], Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), and Manship, Brigitte more...
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Male ,Cancer Research ,Proto-Oncogene Proteins c-jun ,β-Catenin ,Cell ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,urologic and male genital diseases ,Mice ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,DU145 ,Cell Line, Tumor ,Proto-Oncogene Proteins ,medicine ,Gene silencing ,Animals ,Humans ,MEN1 ,Gene Silencing ,RC254-282 ,beta Catenin ,Cell Proliferation ,Cell Nucleus ,Prostate cancer ,Chemistry ,Research ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Prostatic Neoplasms ,Cell migration ,Protein Transport ,medicine.anatomical_structure ,AR-independent cells ,Oncology ,BMI1 ,Cell culture ,Receptors, Androgen ,Catenin ,Cancer research ,Heterografts ,JunD - Abstract
Background Recent studies highlighted the increased frequency of AR-low or -negative prostate cancers (PCas) and the importance of AR-independent mechanisms in driving metastatic castration-resistant PCa (mCRPC) development and progression. Several previous studies have highlighted the involvement of the MEN1 gene in PCa. In the current study, we focused on its role specifically in AR-independent PCa cells. Methods Cell tumorigenic features were evaluated by proliferation assay, foci formation, colony formation in soft agar, wound healing assay and xenograft experiments in mice. Quantitative RT-PCR, Western blot and immunostaining were performed to determine the expression of different factors in human PCa lines. Different ChIP-qPCR-based assays were carried out to dissect the action of JunD and β-catenin. Results We found that MEN1 silencing in AR-independent cell lines, DU145 and PC3, resulted in an increase in anchorage independence and cell migration, accompanied by sustained MYC expression. By searching for factors known to positively regulate MYC expression and play a relevant role in PCa development and progression, we uncovered that MEN1-KD triggered the nuclear translocation of JunD and β-catenin. ChIP and 3C analyses further demonstrated that MEN1-KD led to, on the one hand, augmented binding of JunD to the MYC 5′ enhancer and increased formation of loop structure, and on the other hand, increased binding of β-catenin to the MYC promoter. Moreover, the expression of several molecular markers of EMT, including E-cadherin, BMI1, Twist1 and HIF-1α, was altered in MEN1-KD DU145 and PC3 cells. In addition, analyses using cultured cells and PC3-GFP xenografts in mice demonstrated that JunD and β-catenin are necessary for the altered tumorigenic potential triggered by MEN1 inactivation in AR-independent PCa cells. Finally, we observed a significant negative clinical correlation between MEN1 and CTNNB1 mRNA expression in primary PCa and mCRPC datasets. Conclusions Our current work highlights an unrecognized oncosuppressive role for menin specifically in AR-independent PCa cells, through the activation of JunD and β-catenin pathways. more...
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- 2021
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12. Reduced menin expression leads to decreased ERα expression and is correlated with the occurrence of human luminal B-like and ER-negative breast cancer subtypes
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Romain Teinturier, Chang Xian Zhang, Thomas Bachelot, Laura Corbo, Loay Kassem, Lucie Malbeteau, Yakun Luo, Muriel Le Romancer, Razan Abou Ziki, Isabelle Treilleux, Philippe Bertolino, Samuele Gherardi, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Lutte contre le Cancer Léon Bérard (CLB), and Manship, Brigitte more...
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Hepatocyte Nuclear Factor 3-alpha ,Cancer Research ,congenital, hereditary, and neonatal diseases and abnormalities ,endocrine system ,endocrine system diseases ,[SDV]Life Sciences [q-bio] ,Breast Neoplasms ,Biology ,Mice ,Breast cancer ,Preclinical Study ,Proto-Oncogene Proteins ,GATA3 ,medicine ,Gene silencing ,Animals ,Humans ,MEN1 ,Promoter Regions, Genetic ,ERα ,Reporter gene ,Gene knockdown ,ESR1 ,Estrogen Receptor alpha ,Menin ,medicine.disease ,[SDV] Life Sciences [q-bio] ,Gene Expression Regulation, Neoplastic ,Oncology ,Cancer research ,MCF-7 Cells ,Female ,FOXA1 ,Luminal subtypes ,Estrogen receptor alpha - Abstract
Purpose Menin, encoded by the MEN1 gene, was recently reported to be involved in breast cancers, though the underlying mechanisms remain elusive. In the current study, we sought to further determine its role in mammary cells. Methods Menin expression in mammary lesions from mammary-specific Men1 mutant mice was detected using immunofluorescence staining. RT-qPCR and western blot were performed to determine the role of menin in ERα expression in human breast cancer cell lines. ChIP-qPCR and reporter gene assays were carried out to dissect the action of menin on the proximal ESR1 promoter. Menin expression in female patients with breast cancer was analyzed and its correlation with breast cancer subtypes was investigated. Results Immunofluorescence staining revealed that early mammary neoplasia in Men1 mutant mice displayed weak ERα expression. Furthermore, MEN1 silencing led to both reduced ESR1 mRNA and ERα protein expression in MCF7 and T47D cells. To further dissect the regulation of ESR1 transcription by menin, we examined whether and in which way menin could regulate the proximal ESR1 promoter, which has not been fully explored. Using ChIP analysis and reporter gene assays covering − 2500 bp to + 2000 bp of the TSS position, we showed that the activity of the proximal ESR1 promoter was markedly reduced upon menin downregulation independently of H3K4me3 status. Importantly, by analyzing the expression of menin in 354 human breast cancers, we found that a lower expression was associated with ER-negative breast cancer (P = 0.041). Moreover, among the 294 ER-positive breast cancer samples, reduced menin expression was not only associated with larger tumors (P = 0.01) and higher SBR grades (P = 0.005) but also with the luminal B-like breast cancer subtype (P = 0.006). Consistent with our clinical data, we demonstrated that GATA3 and FOXA1, co-factors in ESR1 regulation, interact physically with menin in MCF7 cells, and MEN1 knockdown led to altered protein expression of GATA3, the latter being a known marker of the luminal A subtype, in MCF7 cells. Conclusion Taken together, our data provide clues to the important role of menin in ERα regulation and the formation of breast cancer subtypes. more...
- Published
- 2021
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13. Men1 disruption in Nkx3.1-deficient mice results in ARlow/CD44+ microinvasive carcinoma development with the dysregulated AR pathway
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Razan Abou Ziki, Romain Teinturier, Virginie Firlej, Nicolas Gadot, Muriel Le Romancer, Samuele Gherardi, Myriam Decaussin-Petrucci, Virginie Vlaeminck-Guillem, Remy Bonnavion, Philippe Bertolino, F. Vacherot, Yakun Luo, Isabelle Goddard, Chang Xian Zhang, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Résistances Thérapeutiques du Cancer de la Prostate (TRePCa), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12) more...
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0301 basic medicine ,endocrine system ,Cancer Research ,endocrine system diseases ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,urologic and male genital diseases ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,DU145 ,LNCaP ,Genetics ,medicine ,Gene silencing ,MEN1 ,Molecular Biology ,ComputingMilieux_MISCELLANEOUS ,Gene knockdown ,biology ,CD44 ,medicine.disease ,Androgen receptor ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein - Abstract
Dysregulated androgen receptor (AR) plays a crucial role in prostate cancer (PCa) development, though further factors involved in its regulation remain to be identified. Recently, paradoxical results were reported on the implication of the MEN1 gene in PCa. To dissect its role in prostate luminal cells, we generated a mouse model with inducible Men1 disruption in Nkx3.1-deficient mice in which mouse prostatic intraepithelial neoplasia (mPIN) occur. Prostate glands from mutant and control mice were analyzed pathologically and molecularly; cellular and molecular analyses were carried out in PCa cell lines after MEN1 knockdown (KD) by siRNA. Double-mutant mice developed accelerated mPIN and later displayed microinvasive adenocarcinoma. Markedly, early-stage lesions exhibited a decreased expression of AR and its target genes, accompanied by reduced CK18 and E-cadherin expression, suggesting a shift from a luminal to a dedifferentiated epithelial phenotype. Intriguingly, over 60% of menin-deficient cells expressed CD44 at a later stage. Furthermore, MEN1 KD led to the increase in CD44 expression in PC3 cells re-expressing AR. Menin bound to the proximal AR promoter and regulated AR transcription via the H3K4me3 histone mark. Interestingly, the cell proliferation of AR-dependent cells (LNCaP, 22Rv1, and VCaP), but not of AR-independent cells (DU145, PC3), responded strongly to MEN1 silencing. Finally, menin expression was found reduced in some human PCa. These findings highlight the regulation of the AR promoter by menin and the crosstalk between menin and the AR pathway. Our data could be useful for better understanding the increasingly reported AR-negative/NE-negative subtype of PCa and the mechanisms underlying its development. more...
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- 2021
- Full Text
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14. MEN1 silencing triggers the dysregulation of mTORC1 and MYC pathways in ER+ breast cancer cells.
- Author
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Ziki, Razan Abou, Teinturier, Romain, Yakun Luo, Cerutti, Catherine, Vanacker, Jean-Marc, Poulard, Coralie, Bachelot, Thomas, Diab-Assaf, Mona, Treilleux, Isabelle, Chang Xian Zhang, and Le Romancer, Muriel more...
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BREAST cancer ,ESTROGEN ,CANCER cells ,EVEROLIMUS ,INVERSE relationships (Mathematics) ,DATA mining ,OVERALL survival - Abstract
Menin, encoded by the MEN1 gene, has been identified as a critical factor regulating ESR1 transcription, playing an oncogenic role in ER+ breast cancer (BC) cells. Here, we further dissected the consequences of menin inactivation in ER+ BC cells by focusing on factors within two major pathways involved in BC, mTOR and MYC. MEN1 silencing in MCF7 and T-47D resulted in an increase in phosphor-p70S6K1, phosphor-p85S6K1 and phosphor-4EBP1 expression. The use of an AKT inhibitor inhibited the activation of S6K1 and S6RP triggered by MEN1 knockdown (KD). Moreover, MEN1 silencing in ER+ BC cells led to increased formation of the eIF4E and 4G complex. Clinical studies showed that patients with menin-low breast cancer receiving tamoxifen plus everolimus displayed a trend toward better overall survival. Importantly, MEN1 KD in MCF7 and T-47D cells led to reduced MYC expression. ChIP analysis demonstrated that menin bound not only to the MYC promoter but also to its 5' enhancer. Furthermore, E2-treated MEN1 KD MCF7 cells displayed a decrease in MYC activation, suggesting its role in estrogen-mediated MYC transcription. Finally, expression data mining in tumors revealed a correlation between the expression of MEN1 mRNA and that of several mTORC1 components and targets and a significant inverse correlation between MEN1 and two MYC inhibitory factors, MYCBP2 and MYCT1, in ER+ BC. The current work thus highlights altered mTORC1 and MYC pathways after menin inactivation in ER+ BC cells, providing insight into the crosstalk between menin, mTORC1 and MYC in ER+ BC. [ABSTRACT FROM AUTHOR] more...
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- 2022
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15. Men1 disruption in Nkx3.1-deficient mice results in AR
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Romain, Teinturier, Yakun, Luo, Myriam, Decaussin-Petrucci, Virginie, Vlaeminck-Guillem, Francis, Vacherot, Virginie, Firlej, Rémy, Bonnavion, Razan, Abou Ziki, Samuele, Gherardi, Isabelle, Goddard, Nicolas, Gadot, Philippe, Bertolino, Muriel, Le Romancer, and Chang Xian, Zhang more...
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Homeodomain Proteins ,Male ,Prostatic Intraepithelial Neoplasia ,Prostate ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,Mice ,Hyaluronan Receptors ,Receptors, Androgen ,Proto-Oncogene Proteins ,Animals ,Humans ,Neoplasm Invasiveness ,Cell Proliferation ,Signal Transduction ,Transcription Factors - Abstract
Dysregulated androgen receptor (AR) plays a crucial role in prostate cancer (PCa) development, though further factors involved in its regulation remain to be identified. Recently, paradoxical results were reported on the implication of the MEN1 gene in PCa. To dissect its role in prostate luminal cells, we generated a mouse model with inducible Men1 disruption in Nkx3.1-deficient mice in which mouse prostatic intraepithelial neoplasia (mPIN) occur. Prostate glands from mutant and control mice were analyzed pathologically and molecularly; cellular and molecular analyses were carried out in PCa cell lines after MEN1 knockdown (KD) by siRNA. Double-mutant mice developed accelerated mPIN and later displayed microinvasive adenocarcinoma. Markedly, early-stage lesions exhibited a decreased expression of AR and its target genes, accompanied by reduced CK18 and E-cadherin expression, suggesting a shift from a luminal to a dedifferentiated epithelial phenotype. Intriguingly, over 60% of menin-deficient cells expressed CD44 at a later stage. Furthermore, MEN1 KD led to the increase in CD44 expression in PC3 cells re-expressing AR. Menin bound to the proximal AR promoter and regulated AR transcription via the H3K4me3 histone mark. Interestingly, the cell proliferation of AR-dependent cells (LNCaP, 22Rv1, and VCaP), but not of AR-independent cells (DU145, PC3), responded strongly to MEN1 silencing. Finally, menin expression was found reduced in some human PCa. These findings highlight the regulation of the AR promoter by menin and the crosstalk between menin and the AR pathway. Our data could be useful for better understanding the increasingly reported AR-negative/NE-negative subtype of PCa and the mechanisms underlying its development. more...
- Published
- 2020
16. Prebiotic Properties of Green and Dark Tea Contribute to Protective Effects in Chemical-Induced Colitis in Mice: A Fecal Microbiota Transplantation Study
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Yan Liu, Yakun Luo, Jun Zhang, Kang Sun, Liang Zeng, Liyong Luo, and Xinghua Wang
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0106 biological sciences ,medicine.medical_treatment ,Inflammation ,Gut flora ,Pharmacology ,digestive system ,01 natural sciences ,Camellia sinensis ,Mice ,fluids and secretions ,medicine ,Animals ,Humans ,Colitis ,Feces ,biology ,Tea ,Plant Extracts ,Prebiotic ,010401 analytical chemistry ,General Chemistry ,Fecal bacteriotherapy ,Fecal Microbiota Transplantation ,medicine.disease ,biology.organism_classification ,0104 chemical sciences ,Gastrointestinal Microbiome ,Prebiotics ,TLR4 ,medicine.symptom ,General Agricultural and Biological Sciences ,Dysbiosis ,010606 plant biology & botany - Abstract
Green and dark tea extract (GTE/DTE) ameliorate chemical-induced colitis in mice; however, the role of gut microbiota in the anticolitis effects of green and dark tea in mice remains unclear. This study aims to explore the role of modulations in gut microbes mediated by green and dark tea in colitis mice by fecal microbiota transplantation (FMT). Our results indicated that GTE and DTE (5 mg/kg bodyweight/day for 4 weeks) exhibited prebiotic effects on the donor mice. Moreover, the FMT treatments (transferring the microbiota daily from the 1 g/kg bodyweight fecal sample to each recipient) indicated that, compared with the fecal microbiota from the normal diet-treated donor mice, the fecal microbiota from the GTE- and DTE-treated donor mice significantly ameliorate colitis-related symptoms (e.g., loss of bodyweight, colonic inflammation, loss of barrier integrity, and gut microbiota dysbiosis) and downregulated the TLR4/MyD88/NF-κB pathway. Collectively, GTE and DTE ameliorate chemical-induced colitis by modulating gut microbiota. more...
- Published
- 2020
17. A fast and simple one-step duplex PCR assay for canine distemper virus (CDV) and canine coronavirus (CCoV) detection
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Lin Liang, Yakun Luo, Jinxiang Li, Shangjin Cui, and Jing Wang
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0301 basic medicine ,040301 veterinary sciences ,Biology ,medicine.disease_cause ,Polymerase Chain Reaction ,Sensitivity and Specificity ,law.invention ,0403 veterinary science ,03 medical and health sciences ,Dogs ,Coronavirus, Canine ,law ,Virology ,Jing wang ,medicine ,Animals ,Distemper ,Canine genetics ,Distemper Virus, Canine ,Polymerase chain reaction ,DNA Primers ,Coronavirus ,Brief Report ,Canine distemper virus CDV ,Canine coronavirus ,04 agricultural and veterinary sciences ,General Medicine ,biology.organism_classification ,Duplex pcr ,030104 developmental biology ,Nucleic acid ,RNA, Viral ,Coronavirus Infections - Abstract
The one-step polymerase chain reaction (one-step PCR) detection assay is an innovative PCR detection method, eliminating nucleic acid extraction steps, in which samples can be directly added to PCR reagents for testing. For simultaneous detection of CDV and CCoV, a sensitive and specific one-step duplex PCR (one-step dPCR) assay was developed with two pairs of primers that were designed based on H and M gene sequences of CDV and CCoV, respectively. The one-step dPCR with optimized detection conditions has high specificity and sensitivity; independent sequencing assays further verified these results. more...
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- 2018
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18. Chemical composition, sensory qualities, and pharmacological properties of primary leaf hawk tea as affected using different processing methods
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Yakun Luo, Liang Zeng, Liyong Luo, Jie Wang, Mengjun Ma, Ting Xu, Yan Liu, and Lei Zhang
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0303 health sciences ,Antioxidant ,030309 nutrition & dietetics ,Chemistry ,medicine.medical_treatment ,food and beverages ,Sensory system ,04 agricultural and veterinary sciences ,040401 food science ,Biochemistry ,Processing methods ,03 medical and health sciences ,Herbal tea ,0404 agricultural biotechnology ,Hepatoprotection ,medicine ,Fermentation ,Alcoholic liver damage ,Food science ,Chemical composition ,Food Science - Abstract
Hawk tea (HT), made from the leaves of Litsea coreana Levl. var. lanuginosa, is a traditional Chinese herbal tea. Different processing methods alter the chemical composition of the HT, which changes the sensory qualities and pharmacological properties. The chemical composition, sensory qualities, antioxidant activities, and potential hepatoprotection (ameliorating acute alcoholic liver damage using a mouse model) of pan-fried (PFHT), sun-dried (SDHT), and fermented hawk tea (FHT) were investigated. PFHT had the highest level of phenolics and flavonoids, followed by SDHT and FHT. The highest levels of total and floral/fruit-like volatiles were observed in FHT, which had the highest overall sensory acceptance using a consumer panel. The PFHT and SDHT showed stronger antioxidant activity than FHT. The HT aqueous extracts showed similar hepatoprotective effects in the mouse model, among which PFHT aqueous extracts were the most effective in suppressing hepatic steatosis. PFHT showed the highest health-promoting value with the highest yield of aqueous extracts and the best protective effects against alcoholic liver damage. more...
- Published
- 2020
- Full Text
- View/download PDF
19. A sensitive duplex nanoparticle-assisted PCR assay for identifying porcine epidemic diarrhea virus and porcine transmissible gastroenteritis virus from clinical specimens
- Author
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Liang Lin, Yu Zhu, Xia Ai, Yu-Dong Cui, Shang-Jin Cui, Yakun Luo, Gui-Hua Wang, and Chunren Wang
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0301 basic medicine ,medicine.medical_specialty ,Swine ,Pcr assay ,Rapid detection ,Polymerase Chain Reaction ,Sensitivity and Specificity ,Article ,Microbiology ,law.invention ,03 medical and health sciences ,Medical microbiology ,law ,N gene ,TGEV ,Virology ,Genetics ,medicine ,Animals ,Molecular Biology ,Polymerase chain reaction ,Swine Diseases ,biology ,Porcine epidemic diarrhea virus ,Transmissible gastroenteritis virus ,PEDV ,General Medicine ,Porcine transmissible gastroenteritis virus ,biology.organism_classification ,Duplex nanoPCR ,Clinical diagnosis ,030104 developmental biology ,Duplex (building) ,Nanoparticles - Abstract
In this study, a novel duplex nanoparticle-assisted polymerase chain reaction (nanoPCR) assay was developed to detect porcine epidemic diarrhea virus (PEDV) and porcine transmissible gastroenteritis virus (TGEV). Two pairs of primers were designed based on the conserved region within the N gene of PEDV and TGEV. In a screening of 114 clinical samples from four provinces in China for PEDV and TGEV, 48.2 and 3.5 % of the samples, respectively, tested positive. Under optimized conditions, the duplex nanoPCR assay had a detection limit of 7.6 × 101 and 8.5 × 101 copies μL−1 for PEDV and TGEV, respectively. The sensitivity of the duplex nanoPCR assay was ten times higher than that of a conventional PCR assay. Moreover, no fragments were amplified when the duplex nanoPCR assay was used to test samples containing other porcine viruses. Our results indicate that the duplex nanoPCR assay described here is useful for the rapid detection of PEDV and TGEV and can be applied in clinical diagnosis. more...
- Published
- 2016
20. Beak and Feather Disease Virus
- Author
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YAKUN LUO
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- 2016
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21. Development and evaluation of the rVP-ELISA for detection of antibodies against porcine parvovirus.
- Author
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Miaomiao Kong, Yonggang Peng, Yuchao Cui, Tiecheng Chang, Xiaoling Wang, Zhaoxia Liu, Yonggang Liu, Yu Zhu, Yakun Luo, Qinghai Tang, Li Feng, and Shangjin Cui
- Subjects
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ENZYME-linked immunosorbent assay , *IMMUNOGLOBULINS , *PARVOVIRUS diseases , *SWINE diseases , *BACULOVIRUSES , *GENE expression in viruses , *HEMAGGLUTINATION tests , *WESTERN immunoblotting - Abstract
The gene encoding the VP2 protein of porcine parvovirus (PPV) was expressed in an insect-baculovirus system. The recombinant (r) VP2 was similar antigenically/functionally to the native capsid protein as demonstrated by hemagglutination (HA), Western blotting using PPV positive sera. The purified rVP2 proteins were used as coating antigen to establish a rVP-ELISA method for detection of PPV positive and negative sera from pigs. The optimal operating conditions of the rVP-ELISA were: the concentration of rVP2 proteins coated on the wells was 2 µg/mL; the diluted concentration of serum was 1: 150 and that of the enzyme-labeled antibody was 1: 6000. A total of 596 sera were detected by this assay, and the average positive rate was 87%. Compared with France LSI kit, the result showed that the coincidence rate was 96.7%. In conclusion, the rVP2-ELISA is a sensitive and specific method for detecting antibodies against PPV. [ABSTRACT FROM AUTHOR] more...
- Published
- 2014
- Full Text
- View/download PDF
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