Olfactory receptors (ORs) are expressed not only in the sensory neurons of the olfactory epithelium, where they detect volatile substances, but also in various other tissues where their potential functions are largely unknown. Here, we report the physiological characterization of human OR51E2, also named prostate-specific G-protein-coupled receptor (PSGR) due to its reported up-regulation in prostate cancer. We identified androstenone derivatives as ligands for the recombinant receptor. PSGR can also be activated with the odorant ␤-ionone. Activation of the endogenous receptor in prostate cancer cells by the identified ligands evoked an intracellular Ca 2؉ increase. Exposure to ␤-ionone resulted in the activation of members of the MAPK family and inhibition of cell proliferation. Our data give support to the hypothesis that because PSGR signaling could reduce growth of prostate cancer cells, specific receptor ligands might therefore be potential candidates for prostate cancer treatment.Excessive signaling by G-protein-coupled receptors (GPCRs) 3 such as endothelin A receptor (1), bradykinin 1 receptor (2), follicle-stimulating hormone receptor (3), and thrombin receptor (4, 5) is known to occur in prostate cancers due to strong overexpression of the respective receptors. Activation of some of these GPCRs results in androgen-independent androgen receptor activation, thus promoting the transition of prostate cancer cells from an androgen-dependent to an androgen-independent state (6, 7).The prostate-specific G-protein-coupled receptor (PSGR) is a class A GPCR that was initially identified as a prostate-specific tumor biomarker (8 -10). It is specifically expressed in prostate epithelial cells, and its expression increases significantly in human prostate intraepithelial neoplasia and prostate tumors, suggesting that PSGR may play an important role in early prostate cancer development and progression (9, 11). Although expression of the human PSGR was found to be prostate-specific (10, 12), mRNA can also be detected in the olfactory zone and the medulla oblongata of the human brain (12). Human PSGR shares 93% amino acid homology to the respective mouse and rat homologues, which are also expressed in the brain (12). Interestingly, PSGR has numerous sequence motifs in common with the large superfamily of olfactory receptors (ORs), which build the largest class of human GPCRs and allow the recognition of a wide range of structurally diverse molecules in the nasal epithelium (13-15). Recently, also the steroid hormones androstenone and androstadienone were identified as OR ligands (16). In addition to their role in the sensory neurons of the nose, ORs have been found in different tissues throughout the body (17,18). Their function(s) in these extranasal locations are questionable except for in a few cases where functional studies have been performed in spermatozoa (19,20) and in enterochromaffin cells of the gastrointestinal tract (21).Here, we report the identification of steroid ligands of heterologously expressed PSGR...

MicroRNAs (miRNAs) are important regulators of plant growth and development. Previously, we identified a group of conserved and novel miRNA families from soybean (Glycine max) roots. Many of these miRNAs are specifically induced during soybean-Bradyrhizobium japonicum interactions. Here, we examined the gene expression levels of six families of novel miRNAs and investigated their functions in nodule development. We used northern-blot analyses to study the tissue specificity and time course of miRNA expression. Transgenic expression of miR482, miR1512, and miR1515 led to significant increases of nodule numbers, while root length, lateral root density, and the number of nodule primordia were not altered in all tested miRNA lines. We also found differential expression of these miRNAs in nonnodulating and supernodulating soybean mutants. The expression levels of 22 predicted target genes regulated by six novel miRNAs were studied by real-time polymerase chain reaction and quantitative real-time polymerase chain reaction. These results suggested that miRNAs play important roles in soybean nodule development.

BackgroundAlternative splicing (AS), as a potent and pervasive mechanism of transcriptional regulatory, expands the genome's coding capacity and involves in the initiation and progression of cancer. Systematic analysis of alternative splicing in colorectal cancer (CRC) is lacking and greatly needed.MethodsRNA-Seq data and corresponding clinical information of CRC cohort were downloaded from the TCGA data portal. Then, a java application, known as SpliceSeq, was used to evaluate the RNA splicing patterns and calculate the Percent Spliced In (PSI) value. Differently expressed AS events (DEAS) were identified based on PSI value between paired CRC and adjacent tissues. DEAS and its splicing networks were further analyzed by bioinformatics methods. Kaplan-Meier, Cox proportional regression and unsupervised clustering analysis were used to evaluate the association between DEAS and patients' clinical features.ResultsAfter strict filtering, a total of 34,334 AS events were identified, among which 421 AS events were found expressed differently. Parent genes of these DEAS play a important role in regulating CRC-related processes such as protein kinase activity (FDR<0.0001), PI3K-Akt signaling pathway (FDR = 0.0024) and p53 signaling pathway (FDR = 0.0143). 37 DEAS events were found to be associated with OS, and 68 DEAS events were found to be associated with DFS. Stratifying patients according to the PSI value of AT in CXCL12 and RI in CSTF3 formed significant Kaplan-Meier curves in both OS and DFS survival analysis. Unsupervised clustering analysis using DEAS revealed four clusters with distinct survival patterns, and associated with consensus molecular subtypes.ConclusionsLarge differences of AS events in CRC appear to exist, and these differences are likely to be important determinants of both prognosis and biological regulation. Our identified CRC-related AS events and uncovered splicing networks are valuable in deciphering the underlying mechanisms of AS in CRC, and provide clues of therapeutic targets to further validations.