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 .

Carboxylate Ligand-supported Agn (n=21 and 24) Alkynyl Clusters Induced by Single/Double Carbonate Ions.

Structural transformation is important for the study of silver cluster compounds, in which controlled synthesis of their shapes and sizes via anion template-driven is one key scientific question. In this work, the CO3 2- anion templates were captured by the [t BuC≡CAg]n system under the stimulation induced by carboxylate ligand CF3 COO- /PhCOO- , and two silver alkynyl clusters [(CO3 2- )@Ag21 (t BuC≡C)16 (CF3 COO)3 (H2 O)]⋅DMF⋅2CH2 Cl2 (1) and [(CO3 2- )2 @Ag24 (t BuC≡C)16 (PhCOO)4 ]⋅CH3 OH⋅4DMF (2) have been successfully isolated and charactered. With the increase of the number of CO3 2- templates from single to double, the outer silver atoms from twenty-one to twenty-four, accompanied by the growth of the cluster skeleton from 9.8 Š×6.9 Šof the (CO3 2- )@Ag21 unit to 10.5 Š×7.3 Šof the (CO3 2- )2 @Ag24 unit. In addition, the syntheses, structures, photocurrent responses, cyclic voltammetry characteristics, luminescence, and photodegradation of compounds 1 and 2 have been studied.

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.

Ferroelectric control of pseudospin texture in CuInP2S6monolayer.

Spin-orbit coupling (SOC) plays an important role in condensed matter physics and has potential applications in spintronics devices. In this paper, we study the electronic properties of ferroelectric CuInP2S6(CIPS) monolayer through first-principles calculations. The result shows that CIPS monolayer is a potential for valleytronics material and we find that the in-plane helical and nonhelical pseudospin texture are induced by the Rashba and Dresselhaus effect, respectively. The chirality of helical pseudospin texture is coupled to the out-of-plane ferroelectric polarization. Furthermore, a large spin splitting due to the SOC effect can be found atKvalley, which can be regarded as the Zeeman effect under a valley-dependent pseudomagnetic field. The CIPS monolayer with Rashbaet aleffects provides a good platform for electrically controlled spin polarization physics.

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.

Inhibition of BRD4 prevents proliferation and epithelial-mesenchymal transition in renal cell carcinoma via NLRP3 inflammasome-induced pyroptosis.

BRD4 has long been implicated in many different pathological processes, in particular, the development of cancer and inflammation. Pyroptosis is a newly recognized type of inflammatory programmed cell death. However, the correlation between BRD4 and pyroptosis in renal cell carcinoma (RCC) remains elusive. The present study demonstrates that BRD4 expression levels are markedly upregulated, while pyroptosis-associated proteins are significantly reduced, in RCC tissues and cells. Inhibition of BRD4, via either genetic knockdown or use of bromodomain inhibitor JQ1, prevented cell proliferation and epithelial-mesenchymal transition (EMT) progression and induced caspase-1-dependent pyroptosis in RCC both in vitro and in vivo. In addition, BRD4 inhibition suppressed proliferation and EMT though pyroptosis in vitro and in vivo. Moreover, NLRP3, which mediates caspase-1-dependent pyroptosis, was increased upon BRD4 inhibition. Furthermore, the transcriptional activity of NLRP3 was enhanced by BRD4 inhibition, and this enhancement was blocked by activation of NF-κB phosphorylation, indicating that NF-κB is an upstream regulator of NLRP3. Collectively, these results show that BRD4 inhibition prevents cell proliferation and EMT, and exerts an antitumor effect in RCC by activating the NF-κB-NLRP3-caspase-1 pyroptosis signaling pathway. Thus, BRD4 is a potential target for RCC treatment, and JQ1 shows promise as a therapeutic agent for this disease.

MiR-142-3p functions as an oncogene in prostate cancer by targeting FOXO1.

Prostate cancer (PCa) is a heterogeneous malignancy, and is a primary cause of cancer-related death in males. Forkhead box transcription factor O1 (FOXO1) exerts antitumor effects in various cancers, including PCa. However, the regulatory mechanism of miR-142-3p on FOXO1 expression in human PCa has not been characterized. In this study, we showed that FOXO1 protein levels were downregulated in PCa tissues and cells. Moreover, FOXO1 expression was a predictor of disease-free survival in patients with PCa and was a predictor of prognosis. Increased expression of FOXO1 suppressed cellular proliferation and induced cell cycle arrest at G0/G1 in vitro. However, FOXO1 mRNA and protein levels were inconsistent in human PCa tissues and cell lines. We showed that miR-142-3p levels were negatively correlated with FOXO1 protein levels in PCa. We also showed that miR-142-3p suppressed FOXO1 expression by directly targeting its 3'-untranslated region. Furthermore, suppression of miR-142-3p inhibited cell proliferation and induced cell cycle arrest, and these effects were blocked by FOXO1 knockdown. In vivo experiments showed that miR-142-3p knockout impaired tumor growth. Our results validate that FOXO1 acted as a tumor suppressor in PCa and demonstrated that FOXO1 was regulated by miR-142-3p, and miR-142-3p may be a potential target for treatment of PCa.