다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

Integrative analysis of 111 reference human epigenomes

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 22 nucleotides, which negatively regulate the gene expression at the post-transcriptional level. This study describes an update of the miRTarBase (http://miRTarBase.mbc.nctu.edu.tw/) that provides information about experimentally validated miRNA-target interactions (MTIs). The latest update of the miRTarBase expanded it to identify systematically Argonaute-miRNA-RNA interactions from 138 crosslinking and immunoprecipitation sequencing (CLIP-seq) data sets that were generated by 21 independent studies. The database contains 4966 articles, 7439 strongly validated MTIs (using reporter assays or western blots) and 348 007 MTIs from CLIP-seq. The number of MTIs in the miRTarBase has increased around 7-fold since the 2014 miRTarBase update. The miRNA and gene expression profiles from The Cancer Genome Atlas (TCGA) are integrated to provide an effective overview of this exponential growth in the miRNA experimental data. These improvements make the miRTarBase one of the more comprehensively annotated, experimentally validated miRNA-target interactions databases and motivate additional miRNA research efforts.

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miRTarBase 2016: updates to the experimentally validated miRNA-target interactions database

Single-cell expression profiles of melanoma Tumors harbor multiple cell types that are thought to play a role in the development of resistance to drug treatments. Tirosh et al. used single-cell sequencing to investigate the distribution of these differing genetic profiles within melanomas. Many cells harbored heterogeneous genetic programs that reflected two different states of genetic expression, one of which was linked to resistance development. Following drug treatment, the resistance-linked expression state was found at a much higher level. Furthermore, the environment of the melanoma cells affected their gene expression programs. Science, this issue p. 189 Melanoma cells show transcriptional heterogeneity. To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, and endothelial cells. Malignant cells within the same tumor displayed transcriptional heterogeneity associated with the cell cycle, spatial context, and a drug-resistance program. In particular, all tumors harbored malignant cells from two distinct transcriptional cell states, such that tumors characterized by high levels of the MITF transcription factor also contained cells with low MITF and elevated levels of the AXL kinase. Single-cell analyses suggested distinct tumor microenvironmental patterns, including cell-to-cell interactions. Analysis of tumor-infiltrating T cells revealed exhaustion programs, their connection to T cell activation and clonal expansion, and their variability across patients. Overall, we begin to unravel the cellular ecosystem of tumors and how single-cell genomics offers insights with implications for both targeted and immune therapies.

Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq

// Dawei Rong 1, * , Handong Sun 3, * , Zhouxiao Li 1 , Shuheng Liu 2 , Chaoxi Dong 1 , Kai Fu 1 , Weiwei Tang 1 and Hongyong Cao 1 1 Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China 2 Department of Neurosurgery, The First affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 3 Department of Oncology Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China * Indicates both are first authors Correspondence to: Hongyong Cao, email: caohongy6167@163.com Weiwei Tang, email: 1243773473twww@sina.com Keywords: circular RNA, back-splicing, microRNA sponge, tumorgenesis Received: February 25, 2017      Accepted: May 01, 2017      Published: July 10, 2017 ABSTRACT Circular RNAs (circRNAs), a novel class of long noncoding RNAs, are characterized by a covalently closed continuous loop without 5’ or 3’ polarities structure and have been widely found in thousands of lives including plants, animals and human beings. Utilizing the high-throughput RNA sequencing (RNA-seq) technology, recent findings have indicated thata great deal of circRNAs, which are endogenous, stable, widely expressed in mammalian cells, often exhibit cell type-specific, tissue-specific or developmental-stage-specific expression. Evidences are arising that some circRNAs might regulate microRNA (miRNA) function as microRNA sponges and play a significant role in transcriptional control. circRNAs associate with related miRNAs and the circRNA-miRNA axes are involved in a serious of disease pathways such as apoptosis, vascularization, invasion and metastasis. In this review, we generalize and analyse the aspects including synthesis, characteristics, classification, and several regulatory functions of circRNAs and highlight the association between circRNAs dysregulation by circRNA-miRNA-mRNA axis and sorts of diseases including cancer- related and non-cancer diseases.”

/pdf/an-emerging-function-of-circrna-mirnas-mrna-axis-in-human-3qn97fazxu.pdf

An emerging function of circRNA-miRNAs-mRNA axis in human diseases.

Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.

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The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects

CircRNA expression profiles for gastric cancer (GC) were screened using plasma samples from 10 GC patients with different TNM stages and 5 healthy individuals as controls Results showed lower expression of circ-KIAA1244 in GC tissues, plasmas, and cells compare to normal controls Further clinical data analysis demonstrated that a decreased expression of circ-KIAA1244 in plasmas was negatively correlated with TNM stage and lymphatic metastasis, and a shorter overall survival time of GC patients Moreover, we found that circ-KIAA1244 could be detected in GC plasma exosomes and showed no obvious significance compared to the expression level in the corresponding plasmas This study revealed a GC-tissues-derived circ-KIAA1244 could serve a novel circulating biomarker for detection of GC

/pdf/circrna-microarray-profiling-identifies-a-novel-circulating-1mkcnbdtqn.pdf

CircRNA microarray profiling identifies a novel circulating biomarker for detection of gastric cancer.

Circular RNAs (circRNAs) are a class of non-coding RNAs with a loop structure, but its functions remain largely unknown. Growing evidence has revealed that circRNAs play a striking role as functional RNAs in the progression of malignant disease. However, the precise role of circRNAs in gastric cancer (GC) remains unclear. CircRNAs were determined by human circRNA array analysis and quantitative reverse transcription polymerase reaction. Luciferase reporter, RNA pull down, and fluorescence in situ hybridization assays were employed to test the interaction between circPSMC3 and miR-296-5p. Ectopic over-expression and siRNA-mediated knockdown of circPSMC3, proliferation, migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPSMC3. CircPSMC3 rather than liner PSMC3 mRNA was down-regulated in GC tissues, corresponding plasmas from GC patients as well as GC cell lines compared to normal controls. Lower circPSMC3 expression in GC patients was correlated with higher TNM stage and shorter overall survival. Over-expression of circPSMC3 and miR-296-5p inhibitor could inhibit the tumorigenesis of gastric cancer cells in vivo and vitro whereas co-transfection of circPSMC3 and miRNA-296-5p could counteract this effect. Importantly, we demonstrated that circPSMC3 could act as a sponge of miR-296-5p to regulate the expression of Phosphatase and Tensin Homolog (PTEN), and further suppress the tumorigenesis of gastric cancer cells. Our study reveals that circPSMC3 can serve as a novel potential circulating biomarker for detection of GC. CircPSMC3 participates in progression of gastric cancer by sponging miRNA-296-5p with PTEN, providing a new insight into the treatment of gastric cancer.

/pdf/circpsmc3-suppresses-the-proliferation-and-metastasis-of-3pmgj53vbw.pdf

CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA through sponging miR-296-5p

Background Circular RNAs (circRNAs) have been found playing important roles in regulating cancer progression. Human circRNA microarray was performed to screen for abnormally expressed circRNA in gastric cancer tissues. In this study, we are aimed to investigate the relationship between a new circular RNA named hsa_circ_0000520 and gastric cancer development. Methods The hsa_circ_0000520 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in gastric tissue, cell and plasma levels, respectively. Then, the association between the expression level of hsa_circ_0000520 and the clinicopathological features of patients with gastric cancer was further analyzed. Finally, a network of hsa_circ_0000520-miRNA-mRNA interactions was predicated. Results In this study, hsa_circ_0000520 was first found to be significantly down-regulated in gastric cancer tissues, plasma and gastric cancer cell lines compared with control cases. Clinicopathological features showed that hsa_circ_0000520 level in GC tissues was negatively associated with TNM stage and in GC plasma linked with CEA expression. Finally, a total of 9 miRNAs and 9 candidate mRNA were predicted to have an interaction with hsa_circ_0000520. Conclusions We first identified that hsa_circ_0000520 was significantly down-regulated in gastric cancer. Our study indicated hsa_circ_0000520 might serve as a novel biomarker for gastric cancer and is involved in gastric carcinoma development.

Dawei Rong

Papers

An emerging function of circRNA-miRNAs-mRNA axis in human diseases.

The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects

CircRNA microarray profiling identifies a novel circulating biomarker for detection of gastric cancer.

CircPSMC3 suppresses the proliferation and metastasis of gastric cancer by acting as a competitive endogenous RNA through sponging miR-296-5p

Hsa_circ_0000520, a potential new circular RNA biomarker, is involved in gastric carcinoma.