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Zhang Z.,Nanjing University | Zha Y.,Nanjing University | Hu W.,Nanjing University | Huang Z.,Nanjing University | And 6 more authors.
Journal of Biological Chemistry | Year: 2013

Background: MicroRNA-21 is important in hepatic fibrosis development, but the mechanism is unclear. Results: MicroRNA-21 is predominantly up-regulated in activated hepatic stellate cells and could form a double negative feedback loop that links fibrogenic machinery. Conclusion: The microRNA-21-mediated loop is a main driving force for hepatic fibrosis progression. Significance: It suggests a mechanism for how microRNA-21 contributes to hepatic fibrosis. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

Liang H.,Jiangsu Engineering Research Center for Micro Biology and Biotechnology
RNA biology | Year: 2013

Communication between cells ensures coordinated behavior. In prokaryotes, this signaling is typically referred to as quorum sensing, whereas in eukaryotic cells, communication occurs through hormones. In recent years, reports have shown that small noncoding RNAs, called microRNAs (miRNAs), can be transmitted from one species to another, inducing signal interference in distant species, even in a cross-kingdom manner. This new mode of cross-species communication might mediate symbiotic and pathogenic relationships between various organisms (e.g., microorganisms and their hosts). Here, we discuss several recent studies concerning miRNA-mediated cross-species gene regulation.

Gu Z.,Jiangsu Engineering Research Center for Micro Biology and Biotechnology | Gu Z.,Nanjing University | Wang J.,Jiangsu Engineering Research Center for Micro Biology and Biotechnology
Bioinformatics | Year: 2013

Summary: CePa is an R package aiming to find significant pathways through network topology information. The package has several advantages compared with current pathway enrichment tools. First, pathway node instead of single gene is taken as the basic unit when analysing networks to meet the fact that genes must be constructed into complexes to hold normal functions. Second, multiple network centralities are applied simultaneously to measure importance of nodes from different aspects to make a full view on the biological system. CePa extends standard pathway enrichment methods, which include both over-representation analysis procedure and gene-set analysis procedure. CePa has been evaluated with high performance on real-world data, and it can provide more information directly related to current biological problems. © 2013 The Author Published by Oxford University Press. All rights reserved.

Zhao S.,Nanjing University | Zhang Y.,Nanjing University | Zheng X.,Nanjing University | Tu X.,Nanjing University | And 5 more authors.
Journal of Cellular Physiology | Year: 2015

Epithelial-to-mesenchymal transition (EMT) has been implicated in embryonic development and various pathological events. However, the involvement of microRNA in the process of EMT remains to be fully defined in hepatocyte. ZEB1 is a well-known transcriptional repressor of E-cadherin and plays a major role in triggering EMT during organ fibrosis and cancer cell metastasis. Computational microRNA target predictions detect a conserved sequence matching to miR-101 in the 3′UTR of ZEB1 mRNA. Our results confirm that miR-101 suppresses ZEB1 expression by targeting the predicted site of ZEB1 3′UTR. Subsequent investigations show that miR-101 is significantly downregulated in the cultured hepatocytes undergoing EMT and in the hepatocytes isolated from fibrotic liver. Along with the loss of miR-101, the ZEB1 expression increases simultaneously in hepatocytes. In addition, miR-101 levels in HCC cell lines are negatively associated with the ZEB1 productions and the metastatic potentials of tumor cells. Mechanistically, we demonstrate that miR-101 significantly inhibits the TGF-β1-induced EMT in hepatocytes, whereas inhibition of miR-101 promotes the EMT process as indicated by the changes of morphology, cell migration, and the expression profiles of EMT markers. In the fibrotic liver, ectopic expression of miR-101 can significantly downregulate ZEB1 in the hepatocyte and thereby reduces the mesenchymal marker expression. Moreover, miR-101 significantly inhibits the proliferation and migration of HCC cell. Our results demonstrate that miR-101 regulates HCC cell phenotype by upregulating the epithelial marker genes and suppressing the mesenchymal ones. © 2015 Wiley Periodicals, Inc.

Li J.,Jiangsu Engineering Research Center for Micro Biology and Biotechnology | Li J.,University of Gottingen | Hua X.,Jiangsu Engineering Research Center for Micro Biology and Biotechnology | Haubrock M.,University of Gottingen | And 2 more authors.
Bioinformatics | Year: 2012

Summary: The great variety of human cell types in morphology and function is due to the diverse gene expression profiles that are governed by the distinctive regulatory networks in different cell types. It is still a challenging task to explain how the regulatory networks achieve the diversity of different cell types. Here, we report on our studies of the design principles of the tissue regulatory system by constructing the regulatory networks of eight human tissues, which subsume the regulatory interactions between transcription factors (TFs), microRNAs (miRNAs) and non-TF target genes. The results show that there are in-/out-hubs of high in-/out-degrees in tissue networks. Some hubs (strong hubs) maintain the hub status in all the tissues where they are expressed, whereas others (weak hubs), in spite of their ubiquitous expression, are hubs only in some tissues. The network motifs are mostly feed-forward loops. Some of them having no miRNAs are the common motifs shared by all tissues, whereas the others containing miRNAs are the tissuespecific ones owned by one or several tissues, indicating that the transcriptional regulation is more conserved across tissues than the post-transcriptional regulation. In particular, a common bow-tie framework was found that underlies the motif instances and shows diverse patterns in different tissues. Such bow-tie framework reflects the utilization efficiency of the regulatory system as well as its high variability in different tissues, and could serve as the model to further understand the structural adaptation of the regulatory system to the specific requirements of different cell functions. © The Author(s) 2012. Published by Oxford University Press.

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