Transcription factors (TFs) are key regulators for gene expression. Here we updated the animal TF database AnimalTFDB to version 2.0 (http://bioinfo.life.hust.edu.cn/AnimalTFDB/). Using the improved prediction pipeline, we identified 72 336 TF genes, 21 053 transcription co-factor genes and 6502 chromatin remodeling factor genes from 65 species covering main animal lineages. Besides the abundant annotations (basic information, gene model, protein functional domain, gene ontology, pathway, protein interaction, ortholog and paralog, etc.) in the previous version, we made several new features and functions in the updated version. These new features are: (i) gene expression from RNA-Seq for nine model species, (ii) gene phenotype information, (iii) multiple sequence alignment of TF DNA-binding domains, and the weblogo and phylogenetic tree based on the alignment, (iv) a TF prediction server to identify new TFs from input sequences and (v) a BLAST server to search against TFs in AnimalTFDB. A new nice web interface was designed for AnimalTFDB 2.0 allowing users to browse and search all data in the database. We aim to maintain the AnimalTFDB as a solid resource for TF identification and studies of transcription regulation and comparative genomics.

The functions of the proto-oncoprotein c-Myc and the tumor suppressor p53 in controlling cell survival and proliferation are inextricably linked as “Yin and Yang” partners in normal cells to maintain tissue homeostasis: c-Myc induces the expression of ARF tumor suppressor (p14ARF in human and p19ARF in mouse) that binds to and inhibits mouse double minute 2 homolog (MDM2) leading to p53 activation, whereas p53 suppresses c-Myc through a combination of mechanisms involving transcriptional inactivation and microRNA-mediated repression. Nonetheless, the regulatory interactions between c-Myc and p53 are not retained by cancer cells as is evident from the often-imbalanced expression of c-Myc over wildtype p53. Although p53 repression in cancer cells is frequently associated with the loss of ARF, we disclose here an alternate mechanism whereby c-Myc inactivates p53 through the actions of the c-Myc-Inducible Long noncoding RNA Inactivating P53 (MILIP). MILIP functions to promote p53 polyubiquitination and turnover by reducing p53 SUMOylation through suppressing tripartite-motif family-like 2 (TRIML2). MILIP upregulation is observed amongst diverse cancer types and is shown to support cell survival, division and tumourigenicity. Thus our results uncover an inhibitory axis targeting p53 through a pan-cancer expressed RNA accomplice that links c-Myc to suppression of p53.

The domestic pig (Sus scrofa) is an important economic animal for meat production and as a suitable model organism for comparative genomics and biomedical studies. In an effort to gain further identification of miRNAs in the pig, we have applied the Illumina Solexa sequencing technology to carry out an in-depth analysis of the miRNA transcriptome in a pool of equal amounts of RNA from 16 different porcine tissues. From this data set, we identified 437 conserved and 86 candidate novel miRNA/miRNA* in the pig, corresponding to 329 miRNA genes. Compared with all the reported porcine miRNAs, the result showed that 112 conserved and 61 candidate novel porcine miRNA were first reported in this study. Further analysis revealed extensive sequence variations (isomiRs) of porcine miRNAs, including terminal isomiRs at both the 5′ and 3′ ends and nucleotide variants. Read counts of individual porcine miRNA spanned from a few reads to approximately 405541 reads, confirming the different level of expression of porcine miRNAs. Subsequently, the tissue expression patterns of 8 miRNAs were characterized by Northern blotting. The results showed that miR-145, miR-423-5p, miR-320, miR-26a, and miR-191 are ubiquitously expressed in diverse tissues, while miR-92, miR-200a, and miR-375 were selectively enriched and expressed in special tissues. Meanwhile, the expression of 8 novel porcine-specific miRNAs was validated by stem-loop RT-PCR, and one of these was detected by Northern blotting. Using the porcine miRNA array designed according to our Solexa results, 123 miRNAs were detected expression in porcine liver tissues. A total of 58 miRNAs showed differential expression between the Tongcheng (a Chinese indigenous fatty breed) and Large White pig breeds (a lean type pig). Taken together, our results add new information to existing data on porcine miRNAs and should be useful for investigating the biological functions of miRNAs in pig and other species.

Protein products of the regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA–DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.

MicroRNAs (miRNAs), a novel class of post-transcriptional gene regulators, have been demonstrated to be involved in several cellular processes regulating the expression of protein-coding genes. To investigate the mechanisms of miRNA-mediated regulation during the process of muscle atrophy, we performed miRNA microarray hybridization between normal differentiated C2C12 cells and dexamethasone (DEX)-treated C2C12 cells. We observed that 11 miRNAs were significantly up-regulated and six miRNAs were down-regulated in the differentiated C2C12 cells after being treated with DEX. Stem-loop real-time RT-PCR confirmed the differential expression of six selected miRNAs (miR-1, miR-147, miR-322, miR-351, and miR-503*, miR-708). miRNA potential target prediction was accomplished using TargetScan, and many target genes related to muscle growth and atrophy have been reported in previous studies. The results of the current study suggested the potential roles of these differentially expressed miRNAs in skeletal muscle atrophy.

AstractBackgroundStreptococcus suis serotype 2 (SS2), a major swine pathogen and an emerging zoonotic agent, has greatly challenged global public health. Systematical information about host immune response to the infection is important for understanding the molecular mechanism of diseases.Results104 and 129 unique genes were significantly up-regulated and down-regulated in the spleens of pigs infected with SS2 (WT). The up-regulated genes were principally related to immune response, such as genes involved in inflammatory response; acute-phase/immune response; cell adhesion and response to stress. The down-regulated genes were mainly involved in transcription, transport, material and energy metabolism which were representative of the reduced vital activity of SS2-influenced cells. Only a few genes showed significantly differential expression when comparing avirulent isogenic strain (ΔHP0197) with mock-infected samples.ConclusionsOur findings indicated that highly pathogenic SS2 could persistently induce cytokines mainly by Toll-like receptor 2 (TLR2) pathway, and the phagocytosis-resistant bacteria could induce high level of cytokines and secrete toxins to destroy deep tissues, and cause meningitis, septicaemia, pneumonia, endocarditis, and arthritis.

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The zinc transporter SLC39A4 influences epithelial cell morphology and migration in various cancers; however, its role in regulating cell invasion and chemotherapeutic resistance in human lung cancer is not yet clear. Here, integrated analysis of gene expression in non-small cell lung cancer revealed that SLC39A4 expression is significantly correlated with increased tumour size and regional lymph node spread, as well as shorter overall survival (OS) and disease-free survival (DFS). SLC39A4 silencing by lentivirus-mediated shRNA blocked human lung cancer cell epithelial-mesenchymal transition and metastasis in vitro and in vivo, respectively. Moreover, SLC39A4 knockdown enhanced cancer cell sensitivity to cisplatin-induced death by inhibiting stemness in lung cancer cells. Collectively, these data suggest that SLC39A4 may be a novel therapeutic target and predictive marker of tumour metastasis in non-small cell lung cancer.