oppOntology: a MATLAB Toolbox for Enrichment Analysis.

Biologists often use systems of ontologies to classify gene lists obtained by high-throughput gene or protein-sequencing instruments, and then enrichment scores were used to rank the ontology system. Therefore, the important molecular functional categories related to the phenotype can be conveniently viewed in the ontology system. Since the birth of GO (Gene Ontology) organization, various types of ontology software have been developed to calculate enrichment scores for the target gene list in the GO system. Herein, we provide an enrichment calculation application oppOntology (Omics Pilot Platform for Ontology) developed by MATLAB. oppOntology supports simultaneous calculation of multiple samples with manifold enrichment scores (GeneCount, GeneRatio, EnrichFactor, HypergeometricTest, and FisherExactTest). oppOntology can not only calculate enrichment scores for generic functional databases, such as GO, KEGG, HPO, and MsigDB, but also for self-defined functional category databases and customized GO Slim. Moreover, oppOntology supports online mapping of KEGG pathway diagrams in a batch way. The GUI (Graphical User Interface) of oppOntology is developed on the architecture of AppDesigner in MATLAB, and all input and output files are Microsoft Excel. oppOntology is an independent, easy-to-use enrichment calculation software, that can be available at https://github.com/HangZhouSheep/oppOntology .

AR-regulated ZIC5 contributes to the aggressiveness of prostate cancer.

The mechanisms by which prostate cancer (PCa) progresses to the aggressive castration-resistant stage remain uncertain. Zinc finger of the cerebellum 5 (ZIC5), a transcription factor belonging to the ZIC family, is involved in the pathology of various cancers. However, the potential effect of ZIC5 on PCa malignant progression has not been fully defined. Here, we show that ZIC5 is upregulated in PCa, particularly in metastatic lesions, in positive association with poor prognosis. Genetic inhibition of ZIC5 in PCa cells obviously attenuated invasion and metastasis and blunted the oncogenic properties of colony formation. Mechanistically, ZIC5 functioned as a transcription factor to promote TWIST1-mediated EMT progression or as a cofactor to strengthen the ß-catenin-TCF4 association and stimulate Wnt/ß-catenin signaling. Importantly, ZIC5 and the androgen receptor (AR) form a positive feed-forward loop to mutually stimulate each other's expression. AR, in cooperation with its steroid receptor coactivator 3 (SRC-3), increased ZIC5 expression through binding to the miR-27b-3p promoter and repressing miR-27b-3p transcription. In turn, ZIC5 potentiated AR, AR-V7, and AR targets' expression. Besides, ZIC5 inhibition reduced AR and AR-V7 protein expression and enhanced the sensitivity of PCa to enzalutamide (Enz) treatment, both in vitro and in vivo. These findings indicate that the reciprocal activation between AR and ZIC5 promotes metastasis and Enz resistance of PCa and suggest the therapeutic value of cotargeting ZIC5 and AR for the treatment of advanced PCa.

opplncRNA: A MATLAB Package for Comprehensive Pathway Analysis of lncRNA-miRNA-mRNA in Humans.

The discovery of new lncRNAs (long noncoding RNAs) and their regulatory pathways has always been a hotspot in the field of ceRNA (competing endogenous RNA). Herein, we report opplncRNA (Omics Pilot Platform of lncRNA), a novel and rapid tool for investigating lncRNA-miRNA-mRNA interactions based on the architecture of MATLAB AppDesigner. opplncRNA is useful to analyze the regulatory interaction networks of lncRNA with a friendly GUI (graphical user interface). There are three lncRNA databases (ENCORI, LncBase, and miRcode) about lncRNA-miRNA interactions that have been integrated into opplncRNA, as well as seven miRNA databases (miRcode, ENCORI, TarBase, miRTarBase, miRDB, miRanda, and miRecords) about miRNA-mRNA interactions as also. opplncRNA can read expression data from any profile techniques, such as microarray or RNA-seq. Then, the relationships between lncRNA-miRNA and miRNA-mRNA can be directly calculated through the profile data of lncRNA, miRNA, and mRNA by the threshold of correlation coefficients. Integrated databases can be used to filter calculation outcomes to obtain more reliable pathways. Moreover, opplncRNA has the functionality of directly demonstrating 3 layers network from lncRNA to mRNA in command line form.

Tumor- and Osteoblast-Derived Periostin in Prostate Cancer bone Metastases.

Exploring the biological function of periostin (POSTN) in prostate cancer (PCa) bone metastasis is of importance. It was observed that the expression of POSTN was high in PCa, especially highest in PCa metastasized to bone. In this study, we found that inhibiting POSTN in PCa cells could significantly alleviate PCa bone metastasis in vivo, suggesting POSTN is a promising therapeutic target. Since, due to the secreted expression of POSTN in osteoblasts and PCa, we hypothesized the positive feedback loop between osteoblasts and PCa mediated by POSTN in PCa bone metastasis. The in vitro experiments demonstrated that osteoblast-derived POSTN promoted PCa cell proliferation and invasion and PCa cell-derived POSTN promotes proliferation of osteoblasts. Furthermore, we found that POSTN regulated PCa and osteoblast function through integrin receptors. Finally, 18F-Alfatide II was used as the molecule probe of integrin αvß3 in PET-CT, revealing high intake in metastatic lesions. Our findings together indicate that targeting POSTN in PCa cells as well as in the osteoblastic may be an effective treatment for PCa bone metastasis.

Hedgehog signalling mediates drug resistance through targeting TAP1 in hepatocellular carcinoma.

Multidrug resistance is one of the reasons for low survival of advanced hepatocellular carcinoma (HCC). Our previous studies indicate that the hedgehog signalling is involved in hepatic carcinogenesis, metastasis and chemo-resistance. The present study aims to uncover molecular mechanisms underlying hepatoma chemo-resistance. TAP1 and GLI1/2 gene expression was assessed in both poorly differentiated hepatoma cells and HCC specimens. Potential GLI-binding site in the TAP1 promoter sequence was validated by molecular assays. Approximately 75% HCC specimens exhibited an elevated expression of hedgehog GLI1 transcription factor compared with adjacent liver tissue. Both GLI1/2 and TAP1 protein levels were significantly elevated in poorly differentiated hepatoma cells. Both Huh-7-trans and Huh-7-DN displayed more karyotypic abnormalities and differential gene expression profiles than their native Huh-7 cells. Sensitivity to Sorafenib, doxorubicin and cisplatin was remarkably improved after either GLI1 or TAP1 gene was inhibited by an RNAi approach or by a specific GLI1/2 inhibitor, GANT61. Further experiments confirmed that hedgehog transcription factor GLI1/2 binds to the TAP1 promoter, indicating that TAP1 is one of GLI1/2 target genes. In conclusion, TAP1 is under direct transcriptional control of the hedgehog signalling. Targeting hedgehog signalling confers a novel insight into alleviating drug resistance in the treatment of refractory HCC.