Cross-cell DNA methylation annotation and analysis for pan-cancer study

Pan-cancer study can uncover cell- and tissue-specific genomic loci and regions with underlying biological functions, as one of fundamental procedures toward precision medicine. We utilized the online curated resource of DNA methylation annotation knowledgebase, to implement the cross-cell interrogation of pan-cancer study of breast cancer. The study revealed genome-wide differentially-methylated loci and regions by the reduced representation bisulfite sequencing profiling. The knowledgebase contains three level of curated information across multiple cancer and normal cells from the ENCODE Consortium. The reference base covers all identified differentially-methylation CpG sites and regions of interest, further annotated gene information, together with tumor suppressor gene and methylation level. Lastly, it includes the inferred functional association network and related Gene Ontology analysis results based on all the tumor suppressor genes identified from the differentially-methylated regions of interest. Our knowledgebase and analysis results provide a thorough reference source for biomedical researchers and clinicians. The cross-cell analysis results are deposited at: http://github.com/gladex/DMAK.

Polyploidy events shaped the expansion of transcription factors in Cucurbitaceae and exploitation of genes for tendril development

Cucurbitaceae is one of the most important plant families distributed worldwide. Transcription factors (TFs) regulate plant growth at the transcription level. Here, we performed a systematic analysis of 42 641 TFs from 63 families in 14 Cucurbitaceae and 10 non-cucurbit species. Whole-genome duplication (WGD) was the dominant event type in almost all Cucurbitaceae plants. The TF families were divided into 1 210 orthogroups (OGs), of which, 112 were unique to Cucurbitaceae. Although the loss of several gene families was detected in Cucurbitaceae, the gene families expanded in five species that experienced a WGD event comparing with grape. Our findings revealed that the recent WGD events that had occurred in Cucurbitaceae played important roles in the expansion of most TF families. The functional enrichment analysis of the genes that significantly expanded or contracted uncovered five gene families, AUX/IAA, NAC, NBS, HB, and NF-YB. Finally, we conducted a comprehensive analysis of the TCP gene family and identified 16 tendril-related (TEN) genes in 11 Cucurbitaceae species. Interestingly, the characteristic sequence changed from CNNFYFP to CNNFYLP in the TEN gene (Bhi06M000087) of Benincasa hispida. Furthermore, we identified a new characteristic sequence, YNN, which could be used for TEN gene exploitation in Cucurbitaceae. In conclusion, this study will serve as a reference for studying the relationship between gene family evolution and genome duplication. Moreover, it will provide rich genetic resources for functional Cucurbitaceae studies in the future

High-quality ice plant reference genome analysis provides insights into genome evolution and allows exploration of genes involved in the transition from C3 to CAM pathways

Ice plant (Mesembryanthemum crystallinum), a member of the Aizoaceae family, is a typical halophyte crop and a model plant for studying the mechanism of transition from C3 photosynthesis to crassulacean acid metabolism (CAM). Here, we report a high-quality chromosome-level ice plant genome sequence. This 98.05% genome sequence is anchored to nine chromosomes, with a total length of 377.97 Mb and an N50 scaffold of 40.45 Mb. Almost half of the genome (48.04%) is composed of repetitive sequences, and 24 234 genes have been annotated. Subsequent to the ancient whole-genome triplication (WGT) that occurred in eudicots, there has been no recent whole-genome duplication (WGD) or WGT in ice plants. However, we detected a novel WGT event that occurred in the same order in Simmondsia chinensis, which was previously overlooked. Our findings revealed that ice plants have undergone chromosome rearrangements and gene removal during evolution. Combined with transcriptome and comparative genomic data and expression verification, we identified several key genes involved in the CAM pathway and constructed a comprehensive network. As the first genome of the Aizoaceae family to be released, this report will provide a rich data resource for comparative and functional genomic studies of Aizoaceae, especially for studies on salt tolerance and C3-to-CAM transitions to improve crop yield and resistance

Formaldehyde-assisted synthesis of ultrathin Rh nanosheets for applications in CO oxidation

National Basic Research Program of China [2011CBA00508]; National Natural Science Foundation of China [21171142]; program for New Century Excellent Talents in University [NCET-11-0294]; Fundamental Research Funds for the Central UniversitiesUltrathin Rh nanosheets with a thickness of approximately 1 nm were synthesized via a simple surfactant-free hydrothermal route, using Rh(II) acetylacetonate as the precursor and formaldehyde as the shape controller. CO and H-2 originating from the formaldehyde decomposition played key roles in the formation of ultrathin Rh nanosheets

IL-1β-Mediated Up-Regulation of WT1D via miR-144-3p and Their Synergistic Effect with NF-κB/COX-2/HIF-1α Pathway on Cell Proliferation in LUAD

Background/Aims: IL-1β is an important mediator of “inflammation-cancer" transformation through IL-1β/NF-κB/COX-2/HIF-1α signaling pathway, whereas certain portion of patients with lung adenocarcinoma (LUAD) still suffer from rapid tumor progression in clinical practice, indicating the occurrence of potential bypass. Methods: Real-time polymerase chain reaction was applied to examine the expressions of mir-144-3p, WT1, NF-κB, COX2 and HIF-1α at the mRNA level in 127 LUAD samples and corresponding adjacent tissues. miR-144-3p mimic and antagormiR were used to trigger activation and suppression of miR-144-3p in A549 cells, respectively. MTT assay and Western blotting analysis were carried out to evaluate the cell proliferation. Stable clones with over-expression or knockdown of WT1 were generated with plasmid or shRNA by lentiviral vector technology in H1568 and H1650 NSCLC cell lines, respectively. Dual luciferase reporter assay was performed to validate the effect of miR-144-3p on WT1D. Xenograft model was established for in vivo experiment, and TCGA data were extracted for validation. Results: miR-144-3p could suppress the WT1D expression at the post-transcriptional level, hence regulating cell proliferation in LUAD. WT1 and COX-2 were independent prognostic factors of LUAD patients. In addition, inhibition of IL-1β/miR-144-3p/WT1D and IL-1β/NF-κB/COX-2/HIF-1α pathways using miR-144-3p mimic and Celecoxib, respectively, displayed synergistic suppressive effect on cell proliferation in LUAD. Conclusion: A de novo IL-1β/miR-144-3p/WT1D axis was involved in proliferative regulation of LUAD. Moreover, simultaneous blockade of both IL-1β/miR-144-3p/WT1D and IL-1β/NF-κB/COX-2/ HIF-1α pathways might have synergistic suppressive effect on cell proliferation in LUAD

Prognostic Significance of miR-181b and miR-21 in Gastric Cancer Patients Treated with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin

Background: The goal of this study is to evaluate the effectiveness of S-1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as potential prognostic biomarkers in gastric cancer patients. The expression of candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE specimens. Experimental Design: Gastric cancer patients with KPS>70 were recruited for the trial. The control group was treated with 400 mg/twice/day Doxifluridine plus i.v. with Oxaliplatin at 130 mg/m 2/first day/4 week cycle. The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus i.v. with Oxaliplatin at 130 mg/m 2/first day/4 week cycle. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs were quantified using real time qRT-PCR expression analysis. Results: The overall objective response rate (CR+PR) of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR) vs. 17.6% (CR+PR) with Doxifluridine/Oxaliplatin for advanced stage gastric cancer patients. The average overall survival for patients treated with S-1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with Doxifluridine/Oxaliplatin. The expression of miR-181b (P = 0.022) and miR-21 (P = 0.0029) was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06-0.45; P = 0.0004) and miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16-0.87; P = 0.018) are closely associated with better patient's overall survival for both S-1 and Doxifluridine based regimens. Conclusion: Patients treated with S-1/Oxaliplatin had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer. © 2011 Jiang et al