研究成果

Dissemination is an ominous feature of cancer to cause poor prognosis. Formation of tumor satellites is the first step, which is closely interdependent on the factors originating from surrounding niche. Because of lacking appropriate modeling, most studies focusing on cancer-environmental interaction depend on the static pathological analyses of specimens. Using the biomimicking system capable of inducing tumor satellite formation in vitro, the niche factors were explored for their influence on cancer budding. Our results demonstrated the real-time dynamic of tumor satellite formation of head and neck squamous cell carcinoma (HNSCC) that was significantly affected by these niche factors. Hypoxia reduced the incidence and migratory distance of HNSCC tumor satellites via decreasing the...

Intrahepatic cholangiocarcinoma (ICC) is characterized by fibrous stroma and clinical behavior more aggressive than that of hepatocellular carcinoma (HCC). Scirrhous HCC is a subtype of HCC with fibrous stroma, frequently has partial cholangiocytic differentiation, and is more likely to have an aggressive behavior. This study explored the interaction of liver cancer cells with the extracellular matrix. Liver cancer cells grown on collagen 1-coated plates showed upregulation of cholangiocytic marker expression but downregulation of hepatocytic marker expression. Three-dimensional sphere culture and Boyden chamber assay showed enhanced invasion and migration ability in collagen 1-conditioned liver cancer cells. Interaction with collagen 1 reduced liver cancer cell proliferation. RNA...

Skin epidermis secretes apical extracellular matrix (aECM) as a protective barrier from the external environment. The aECM is highly dynamic and constantly undergoes remodeling during animal development. How aECM dynamics is temporally regulated during development, and whether and how its mis-regulation may impact epidermal cell morphology or function remains to be fully elucidated. Here, we report that the conserved Zn-finger transcription factor BLMP-1/Blimp1, which regulates epidermal development in C. elegans, controls apical cell shape of the epidermis by downregulation of aECM remodeling. Loss of blmp-1 causes upregulation of genes essential for molting, including bus-8 and mlt-8, in adult, leading to an abnormal shape in the apical region of adult epidermal cells. The apical...

The tumor microenvironment (TME), which comprises cellular and noncellular components, is involved in the complex process of cancer development. Emerging evidence suggests that mesenchymal stem cells (MSCs), one of the vital regulators of the TME, foster tumor progression through paracrine secretion. However, the comprehensive phosphosignaling pathways that are mediated by MSC-secreting factors have not yet been fully established. In this study, we attempt to dissect the MSC-triggered mechanism in lung cancer using quantitative phosphoproteomics. A total of 1958 phosphorylation sites are identified in lung cancer cells stimulated with MSC-conditioned medium. Integrative analysis of the identified phosphoproteins and predicted kinases demonstrates that MSC-conditioned medium functionally...

The plasticity along the epithelial-mesenchymal transition (EMT) spectrum has been shown to be regulated by various epigenetic repertoires. Emerging evidence of local chromatin conformation changes suggests that regulation of EMT may occur at a higher order of three-dimensional genome level. We perform Hi-C analysis and combine ChIP-seq data across cancer cell lines representing different EMT states. We demonstrate that the epithelial and mesenchymal genes are regulated distinctively. We find that EMT genes are regulated within their topologically associated domains (TADs), with only a subset of mesenchymal genes being influenced by A/B compartment switches, indicating topological remodeling is required in the transcriptional regulation of these genes. At the TAD level, epithelial and...

Increased pancreatic cancer incidence has been observed among younger than in older adults. This pilot study aimed to determine the feasibility of a large study that would compare the age at diagnosis of pancreatic cancer among patients with different risk factors. We compared the age at diagnosis of pancreatic cancer between groups of pancreatic cancer patients exposed and not exposed to the identified risk factors. We estimated the age at which exposure started, average exposure quantity, and total years of exposure and investigated their relationships with age at diagnosis of pancreatic cancer. Sixteen out of 24 (67%) subjects carried known genetic factors and/or had smoking and/or drinking habits; however, an earlier age of pancreatic cancer diagnosis was not observed. Conversely, we...

With the proliferation of genomic sequence data for biomedical research, the exploration of human genetic information by domain experts requires a comprehensive interrogation of large numbers of scientific publications in PubMed. However, a query in PubMed essentially provides search results sorted only by the date of publication. A search engine for retrieving and interpreting complex relations between biomedical concepts in scientific publications remains lacking. Here, we present pubmedKB, a web server designed to extract and visualize semantic relationships between four biomedical entity types: variants, genes, diseases, and chemicals. pubmedKB uses state-of-the-art natural language processing techniques to extract semantic relations from the large number of PubMed abstracts...

Circular RNAs (circRNAs) are a class of non-coding RNAs formed by pre-mRNA back-splicing, which are widely expressed in animal/plant cells and often play an important role in regulating microRNA (miRNA) activities. While numerous databases have collected a large amount of predicted circRNA candidates and provided the corresponding circRNA-regulated interactions, a stand-alone package for constructing circRNA-miRNA-mRNA interactions based on user-identified circRNAs across species is lacking. We present CircMiMi (circRNA-miRNA-mRNA interactions), a modular, Python-based software to identify circRNA-miRNA-mRNA interactions across 18 species (including 16 animals and 2 plants) with the given coordinates of circRNA junctions. The CircMiMi-constructed circRNA-miRNA-mRNA interactions are...

Post-COVID-19 pulmonary fibrosis (PCPF) is a long-term complication that appears in some COVID-19 survivors. However, there are currently limited options for treating PCPF patients. To address this problem, we investigated COVID-19 patients' transcriptome at single-cell resolution and combined biological network analyses to repurpose the drugs treating PCPF. We revealed a novel gene signature of PCPF. The signature is functionally associated with the viral infection and lung fibrosis. Further, the signature has good performance in diagnosing and assessing pulmonary fibrosis. Next, we applied a network-based drug repurposing method to explore novel treatments for PCPF. By quantifying the proximity between the drug targets and the signature in the interactome, we identified several...

Single-cell transcriptomic data identifies major activation paths of monocyte-derived macrophages as a framework for inflammatory tissue macrophages.