Motivation: Understanding the complexity in gene–phenotype relationship is vital for revealing the genetic basis of common diseases. Recent studies on the basis of human interactome and phenome not only uncovers prevalent phenotypic overlap and genetic overlap between diseases, but also reveals a modular organization of the genetic landscape of human diseases, providing new opportunities to reduce the complexity in dissecting the gene–phenotype association.
Results: We provide systematic and quantitative evidence that phenotypic overlap implies genetic overlap. With these results, we perform the first heterogeneous alignment of human interactome and phenome via a network alignment technique and identify 39 disease families with corresponding causative gene networks. Finally, we propose AlignPI, an alignment-based framework to predict disease genes, and identify plausible candidates for 70 diseases. Our method scales well to the whole genome, as demonstrated by prioritizing 6154 genes across 37 chromosome regions for Crohn's disease (CD). Results are consistent with a recent meta-analysis of genome-wide association studies for CD.
Availability: Bi-modules and disease gene predictions are freely available at the URL http://bioinfo.au.tsinghua.edu.cn/alignpi/
Contact: ruijiang@tsinghua.edu.cn
Supplementary information: Supplementary data are available at Bioinformatics online.
Ovarian cancer accounts for the major part of the mortality attributable to female reproductive system malignant tumors worldwide. Recently, the incidence of ovarian cancer has been increasing annually, and there remains a lack of suitable treatment methods that can significantly improve the 5-year survival rates of patients. Therefore, it is necessary to identify more effective treatments for ovarian cancer. It is established that microRNAs (miRNAs) have important roles in the diagnosis and treatment of ovarian cancer and a specific miRNA, miR-762, can promote the development of a variety of tumors. Menin is encoded by MEN1, a tumor suppressor gene, that is usually downregulated in ovarian cancer. In this study, we evaluated the expression levels of miR-762 and menin in ovarian cancer tissues and demonstrated that they were correlated. In addition, we found that miR-762 can downregulate the expression of menin through a binding site in its 3′-UTR and consequently upregulate the Wnt cell signaling pathway to promote the development of ovarian cancer. These results indicate that miR-762 is a promising potential target for the treatment of ovarian cancer.
The overexpression of CFL1 in ESCs is associated with enhanced proliferation, adhesion, invasion and angiogenesis and reduced apoptosis in EMs. These malignant-like behaviours of ESCs in EMs can be attenuated by inducing CFL1 gene silencing with shRNA interference.
Digestive endoscopy is an important technique for the diagnosis and treatment of digestive system disease. To assure medical safety, a digestive endoscope must be cleaned and disinfected before its use in an operation on the next patient. The most common treatment procedure on a digestive endoscope is high-level disinfection. The potential risk associated with digestive endoscopes is always the focus of endoscopic management in clinical practice. In this study, a polluted pancreatic and biliary endoscope after surgery was cleaned and disinfected multiple times with the standard procedure but still tested positive for Pseudomonas aeruginosa culture, which is very rare and has not been reported in China or abroad.
The Rab GTPase family protein Rab14 has been implicated in cancer development. However, its clinical significance in ovarian cancers and its biological effects have not been examined. The present study aims to examine the clinical significance, biological roles, and molecular mechanism of Rab14 in ovarian cancer progression. We examined expression pattern of Rab14 in 122 cases of ovarian cancer specimens using immunohistochemistry and found Rab14 overexpression correlated with FIGO stage (p = 0.0041). We depleted Rab14 in SKOV3 cells using siRNA and overexpressed Rab14 in SW626 cells. Knockdown of Rab14 inhibited cell growth and invasion while its overexpression facilitated cell growth and invasion. In addition, Rab14 overexpression increased paclitaxel resistance in SW626 cells while its depletion reduced drug resistance. Then, we investigated the role of Rab14 in the regulation of WNT/β-catenin signaling, demonstrating Rab14 overexpression regulated GSK3β phosphorylation and nuclear β-catenin accumulation. Rab14 depletion inhibited while its overexpression enhanced TCF transcriptional activity with corresponding change of Wnt target genes including MMP7 and c-myc. Wnt inhibitor abolished the effect of Rab14 on cell proliferation and Wnt target genes. In conclusion, the present study demonstrated that Rab14 promotes aggressiveness of ovarian cancer cell through, at least partly, Wnt signaling pathway.
It has been previously demonstrated that microRNA (miR)-25 plays critical roles in collagen deposition. Ischemia/reperfusion injury to the myocardium results in fibrosis and collagen deposition. However, whether miR-25 is involved in the development of hypoxia/reoxygenation (H/R)‑induced fibrosis in cardiomyocytes or not remains largely unknown. For this purpose, in the present study, cardiomyocyte H9c2 cells were subjected to H/R. The techniques of flow cytometry, western blot analysis and RT-qPCR were used and we observed increases in the cell apoptosis rate and fibrosis as well as blocking of the cell cycle in the G1 phase. Moreover, the expression of miR-25 was downregulated after H/R and high‑mobility group box 1 (HMGB1) expression was increased. We also found that the overexpression of miR-25 under conditions of H/R inhibited fibrosis and cell apoptosis as well as reversing the cell cycle blocking. Additionally, the targeting of HMGB1 by miR-25 was confirmed by a dual‑luciferase reporter gene assay. Moreover, the effects of miR-25 were further enhanced by a transforming growth factor-β1 (TGF-β1)/Smad3 inhibitor, SB431542, as fibrosis was reduced and apoptosis was suppressed. In conclusion, the protective effects of miR-25 against H/R-induced fibrosis and apoptosis H9c2 cells were due to direct targeting of HMGB1 through the downregulation of the TGF-β1/Smad3 signaling pathway.
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