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Han Z.-G.,Shanghai JiaoTong University | Han Z.-G.,Chinese National Human Genome Center at Shanghai
Annual Review of Genomics and Human Genetics | Year: 2012

Liver cancer is the sixth-most-common cancer overall but the third-most-frequent cause of cancer death. Among primary liver cancers, hepatocellular carcinoma (HCC), the major histological subtype, is associated with multiple risk factors, including hepatitis B and C virus infection, alcohol consumption, obesity, and diet contamination. Although previous studies have revealed that certain genetic and epigenetic changes, such as TP53 and β-catenin mutations, occur in HCC cells, the pathogenesis of this cancer remains obscure. Functional genomic approaches-including genome-wide association studies, whole-genome and whole-exome sequencing, array-based comparative genomic hybridization, global DNA methylome mapping, and gene or noncoding RNA expression profiling-have recently been applied to HCC patients with different clinical features to uncover the genetic risk factors and underlying molecular mechanisms involved in this cancer's initiation and progression. The genome-wide analysis of germline and somatic genetic and epigenetic events facilitates understanding of the pathogenesis and molecular classification of liver cancer as well as the identification of novel diagnostic biomarkers and therapeutic targets for cancer. © 2012 by Annual Reviews. All rights reserved.

Zhang J.,Shanghai JiaoTong University | Zhang J.,Shanghai Key Laboratory of Stomatology | Sun Q.,Shanghai JiaoTong University | Zhang Z.,Shanghai JiaoTong University | And 6 more authors.
Oncogene | Year: 2013

Dysregulated microRNAs (miRNAs) have an important role in many malignant tumors. However, elucidating the roles of miRNAs in cancer biology, especially in epithelial cancers, remains an ongoing process. In this study, we show that both miR-143 and miR-145, which belong to the same miRNA cluster, can negatively modulate expression of their target gene, MDM2. The miR-143 and miR-145 is posttranscriptionally activated by upregulated p53, thereby generating a short miRNAs-MDM2-p53 feedback loop. Re-expression of these miRNAs suppresses cellular growth and triggers the apoptosis of epithelial cancer, in vitro and in vivo, by enhancing p53 activity via MDM2 turnover. Moreover, the miRNA-dependent MDM2 turnover contributes to the equilibrium of repeated p53 pulses in response to DNA damage stress. These findings suggest that MDM2 dysregulation caused by downregulation of miR-143 and miR-145 contributes to epithelial cancer development and has a key role in regulating cellular proliferation and apoptosis. Re-expression of miR-143 and miR-145 may be a reasonable strategy for treatment of epithelial cancers. © 2013 Macmillan Publishers Limited.

Chen N.,CAS Shanghai Institute of Applied Physics | He Y.,Soochow University of China | Su Y.,CAS Shanghai Institute of Applied Physics | Su Y.,Soochow University of China | And 6 more authors.
Biomaterials | Year: 2012

Semiconductor Quantum dots (QDs) have raised great attention because of their superior optical properties and wide utilization in biological and biomedical studies. More recently, there have been intense concerns on cytotoxicity assessment of QDs. Most QDs are made of heavy metal ions (e.g., Cd 2+), which may result in potential in vitro toxicity that hampers their practical applications. In this article, we aim to summarize recent progress on mechanistic studies of cytotoxicity of II-IV QDs. We have studied the cytotoxicity of a series of aqueous synthesized QDs (aqQDs), i.e. CdTe, CdTe/CdS core-shell structured and CdTe/CdS/ZnS core-shell-shell structured aqQDs. Our results suggested that released cadmium ions are responsible for the observed cytotoxicity of cadmium-based QDs. The fact that CdTe/CdS/ZnS core-shell-shell structured QDs are nearly nontoxic to cells further confirmed the role of released cadmium ions on cytotoxicity, and the effective protection of the ZnS shell. However, intracellular level of Cd 2+ ions cannot be the only reason since the comparison with CdCl 2-treated cells suggests there are other factors contributed to the cytotoxicity of aqQDs. Our studies on genome-wide gene expression profiling and subcellular localization of aqQDs with synchrotron-based scanning transmission X-ray microscopy (STXM) further suggest that the cytotoxicity of CdTe QDs not only comes from the release of Cd 2+ ions but also intracellular distribution of QD nanoparticles in cells and the associated nanoscale effects. © 2011 Elsevier Ltd.

Jin W.,Chinese Academy of Sciences | Wang S.,Harvard University | Wang H.,Chinese National Human Genome Center at Shanghai | Jin L.,Fudan University | Xu S.,Chinese Academy of Sciences
American Journal of Human Genetics | Year: 2012

The processes of genetic admixture determine the haplotype structure and linkage disequilibrium patterns of the admixed population, which is important for medical and evolutionary studies. However, most previous studies do not consider the inherent complexity of admixture processes. Here we proposed two approaches to explore population admixture dynamics, and we demonstrated, by analyzing genome-wide empirical and simulated data, that the approach based on the distribution of chromosomal segments of distinct ancestry (CSDAs) was more powerful than that based on the distribution of individual ancestry proportions. Analysis of 1,890 African Americans showed that a continuous gene flow model, in which the African American population continuously received gene flow from European populations over about 14 generations, best explained the admixture dynamics of African Americans among several putative models. Interestingly, we observed that some African Americans had much more European ancestry than the simulated samples, indicating substructures of local ancestries in African Americans that could have been caused by individuals from some particular lineages having repeatedly admixed with people of European ancestry. In contrast, the admixture dynamics of Mexicans could be explained by a gradual admixture model in which the Mexican population continuously received gene flow from both European and Amerindian populations over about 24 generations. Our results also indicated that recent gene flows from Sub-Saharan Africans have contributed to the gene pool of Middle Eastern populations such as Mozabite, Bedouin, and Palestinian. In summary, this study not only provides approaches to explore population admixture dynamics, but also advances our understanding on population history of African Americans, Mexicans, and Middle Eastern populations. © 2012 The American Society of Human Genetics.

Wang W.,Shanghai Ocean University | Wu X.,Shanghai Ocean University | Liu Z.,Shanghai Ocean University | Zheng H.,Chinese National Human Genome Center at Shanghai | Cheng Y.,Shanghai Ocean University
PLoS ONE | Year: 2014

The crustacean hepatopancreas has different functions including absorption, storage of nutrients and vitellogenesis during growth, and ovarian development. However, genetic information on the biological functions of the crustacean hepatopancreas during such processes is limited. The swimming crab, Portunus trituberculatus, is a commercially important species for both aquaculture and fisheries in the Asia-Pacific region. This study compared the transcriptome in the hepatopancreas of female P. trituberculatus during the growth and ovarian maturation stages by 454 high-throughput pyrosequencing and bioinformatics. The goal was to discover genes in the hepatopancreas involved in food digestion, nutrition metabolism and ovarian development, and to identify patterns of gene expression during growth and ovarian maturation. Our transcriptome produced 303,450 reads with an average length of 351 bp, and the high quality reads were assembled into 21,635 contigs and 31,844 singlets. Based on BLASTP searches of the deduced protein sequences, there were 7,762 contigs and 4,098 singlets with functional annotation. Further analysis revealed 33,427 unigenes with ORFs, including 17,388 contigs and 16,039 singlets in the hepatopancreas, while only 7,954 unigenes (5,691 contigs and 2,263 singlets) with the predicted protein sequences were annotated with biological functions. The deduced protein sequences were assigned to 3,734 GO terms, 25 COG categories and 294 specific pathways. Furthermore, there were 14, 534, and 22 identified unigenes involved in food digestion, nutrition metabolism and ovarian development, respectively. 212 differentially expressed genes (DEGs) were found between the growth and endogenous stage of the hepatopancreas, while there were 382 DEGs between the endogenous and exogenous stage hepatopancreas. Our results not only enhance the understanding of crustacean hepatopancreatic functions during growth and ovarian development, but also represent a basis for further research on new genes and functional genomics of P. trituberculatus or closely related species. © 2014 Wang et al.

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