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期刊论文 6

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2023 1

2022 2

2016 2

2010 1

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CO2利用 1

宏转录组 1

微生物电化学技术 1

生物阴极 1

胞外电子传递 1

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Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation

《医学前沿（英文）》 2022年 第16卷 第4期   页码 627-636 doi: 10.1007/s11684-020-0815-4

摘要： Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

关键词： RUNX1     gene mutation     acute myeloid leukemia     transcriptional repression     DNA methylation    

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Development of a dual temperature control system for isoprene biosynthesis in

《化学科学与工程前沿（英文）》 2022年 第16卷 第7期   页码 1079-1089 doi: 10.1007/s11705-021-2088-0

摘要： Conflict between cell growth and product accumulation is frequently encountered in the biosynthesis of secondary metabolites. To address the growth-production conflict in yeast strains harboring the isoprene synthetic pathway in the mitochondria, the dynamic control of isoprene biosynthesis was explored. A dual temperature regulation system was developed through engineering and expression regulation of the transcriptional activator Gal4p. A cold-sensitive mutant, Gal4ep19, was created by directed evolution of Gal4p based on an internally developed growth-based high-throughput screening method and expressed under the heat-shock promoter PSSA4 to control the expression of PGAL-driven pathway genes in the mitochondria. Compared to the control strain with constitutively expressed wild-type Gal4p, the dual temperature regulation strategy led to 34.5% and 72% improvements in cell growth and isoprene production, respectively. This study reports the creation of the first cold-sensitive variants of Gal4p by directed evolution and provides a dual temperature control system for yeast engineering that may also be conducive to the biosynthesis of other high-value natural products.

关键词： transcriptional activator     directed evolution     dynamic control     heat-shock     isoprene    

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Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 183-190 doi: 10.1007/s11684-016-0440-4

摘要：

We performed weighted gene coexpression network analysis (WGCNA) to gain insights into the molecular aspects of hepatocellular carcinoma (HCC). Raw microarray datasets (including 488 samples) were downloaded from the Gene Expression Omnibus (GEO) website. Data were normalized using the RMA algorithm. We utilized the WGCNA to identify the coexpressed genes (modules) after non-specific filtering. Correlation and survival analyses were conducted using the modules, and gene ontology (GO) enrichment was applied to explore the possible mechanisms. Eight distinct modules were identified by the WGCNA. Pink and red modules were associated with liver function, whereas turquoise and black modules were inversely correlated with tumor staging. Poor outcomes were found in the low expression group in the turquoise module and in the high expression group in the red module. In addition, GO enrichment analysis suggested that inflammation, immune, virus-related, and interferon-mediated pathways were enriched in the turquoise module. Several potential biomarkers, such as cyclin-dependent kinase 1 (CDK1), topoisomerase 2α (TOP2A), and serpin peptidase inhibitor clade C (antithrombin) member 1 (SERPINC1), were also identified. In conclusion, gene signatures identified from the genome-based assays could contribute to HCC stratification. WGCNA was able to identify significant groups of genes associated with cancer prognosis.

关键词： hepatocellular carcinoma     coexpression     module     microarray     prognosis    

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Repression of CDKN2C caused by PML/RARα binding promotes the proliferation and differentiation block

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 420-429 doi: 10.1007/s11684-016-0478-3

摘要：

Inappropriate cell proliferation during oncogenesis is often accompanied by inactivation of components involved in the cell cycle machinery. Here, we report that cyclin-dependent kinase inhibitor 2C (CDKN2C) as a member of the cyclin-dependent kinase inhibitors is a target of the PML/RARα oncofusion protein in leukemogenesis of acute promyelocytic leukemia (APL). We found that CDKN2C was markedly downregulated in APL blasts compared with normal promyelocytes. Chromatin immunoprecipitation combined with quantitative polymerase chain reaction demonstrated that PML/RARα directly bound to the CDKN2C promoter in the APL patient-derived cell line NB4. Luciferase assays indicated that PML/RARα inhibited the CDKN2C promoter activity in a dose-dependent manner. Furthermore, all-trans retinoic acid treatment induced CDKN2C expression by releasing the PML/RARα binding on chromatin in NB4 cells. Functional studies showed that ectopic expression of CDKN2C induced a cell cycle arrest at the G0/G1 phase and a partial differentiation in NB4 cells. Finally, the transcriptional regulation of CDKN2C was validated in primary APL patient samples. Collectively, this study highlights the importance of CDKN2C inactivation in the abnormal cell cycle progression and differentiation block of APL cells and may provide new insights into the study of pathogenesis and targeted therapy of APL.

关键词： CDKN2C     acute promyelocytic leukemia     cell cycle arrest     differentiation    

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Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas

Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 399-411 doi: 10.1007/s11684-010-0170-y

摘要： β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway. In our study, we found that, in the development of hepatocellular carcinoma (HCC), β-catenin was correlated with hepatitis B virus (HBV) X gene encoded protein, which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis. The expression levels of wild-type β-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein (HBx), accompanied by destabilization of adherens junction. Reverse transcriptase PCR (RT-PCR), Northern and Western blot showed that reduction of wild-type β-catenin expression involved degradation of the protein. However, RNA interference (RNAi) and luciferase assay indicated that HBx enhanced β-catenin mediated signaling in HepG2 cells. In addition, immunohistochemical and Western blot analysis of β-catenin revealed that a decrease in the β-catenin protein level was found in 58.3% of HBV-related HCCs 19.2% of non-HBV-related tumors. Our data suggest that the expression of HBx contributed to the development of HCC, in part, by repressing the wild-type β-catenin expression and enforcing β-catenin-dependent signaling pathway, thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.

关键词： hepatocellular carcinoma     hepatitis B virus X protein     β     -catenin     cell adhesion     E-cadherin     transcriptional activation    

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流动电极微生物电合成提高产物生成速率及降低能量消耗 Article

褚娜, 王东麟, 王厚锋, 梁勤军, 常佳丽, 高瑜, 蒋永, 曾建雄

《工程（英文）》 2023年 第25卷 第6期   页码 157-167 doi: 10.1016/j.eng.2021.09.015

摘要：

微生物电合成（microbial electrosynthesis, MES）利用可再生电力驱动微生物固定CO2合成化学品，在推进碳循环经济中具有一定潜力，受到广泛关注。但是，很少有研究通过高效反应器设计来促进产乙酸并降低能耗。本研究中，新型流动电极MES反应器的总产乙酸速率[(16 ± 1) g·m−2·d−1]比无粉末活性炭（powder activated carbon, PAC）对照[(8 ± 3) g·m−2·d−1]高两倍。流动电极MES反应器的库伦效率为43.5% ± 3.1%，能量消耗为(0.020 ± 0.005) kWh·g−1，产乙酸的能量效率为18.7% ± 1.3%。基于PAC的流动电极能够降低水跨膜通量、传质阻力，但是对装置电压、流变行为、乙酸吸附的影响较小。流动电极MES反应器中，能量代谢相关基因高表达，Acetobacterium的丰度增加。MES反应器中同时存在用于碳固定的还原性乙酰辅酶A途径（Wood–Ljungdahl pathway, WLP）与还原性三羧酸循环途径（reductive citric acid cycle, rTCA）。堆叠型流动电极MES中的乙酸浓度达7.0 g·L−1。本研究提供一种构建可扩展MES反应器的新方法，促进CO2利用以及产物生成。

关键词： CO2利用     生物阴极     宏转录组     微生物电化学技术     胞外电子传递    

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标题 作者 时间 类型 操作

Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation

期刊论文

Development of a dual temperature control system for isoprene biosynthesis in

期刊论文

Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis

null

期刊论文

Repression of CDKN2C caused by PML/RARα binding promotes the proliferation and differentiation block

null

期刊论文

Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas

Lei CHEN, Liang HU, Liang LI, Yuan LIU, Qian-Qian TU, Yan-Xin CHANG, He-Xin YAN, Meng-Chao WU, Hong-Yang WANG,

期刊论文

流动电极微生物电合成提高产物生成速率及降低能量消耗

褚娜, 王东麟, 王厚锋, 梁勤军, 常佳丽, 高瑜, 蒋永, 曾建雄

期刊论文