Recently, more and more evidence are rapidly accumulating that long noncoding RNAs (lncRNAs) are involved in human tumorigenesis and misregulated in many cancers, including colon cancer. LncRNA could regulate essential pathways that contribute to tumor initiation and progression with their tissue specificity, which indicates that lncRNA would be valuable biomarkers and therapeutic targets. Colon cancer-associated transcript 1 (CCAT1) is a 2628 nucleotide-lncRNA and located in the vicinity of a well-known transcription factor c-Myc. CCAT1 has been found to be upregulated in many cancers, including gastric carcinoma and colonic adenoma-carcinoma. However, its roles in colon cancer are still not well documented and need to be investigated. In this study, we aim to investigate the prognostic value and biological function of CCAT1 and discover which factors may contribute to the deregulation of CCAT1 in colon cancer. Our results revealed that CCAT1 was significantly overexpressed in colon cancer tissues when compared with normal tissues, and its increased expression was correlated with patients' clinical stage, lymph nodes metastasis, and survival time after surgery. Moreover, c-Myc could promote CCAT1 transcription by directly binding to its promoter region, and upregulation of CCAT1 expression in colon cancer cells promoted cell proliferation and invasion. These data suggest that c-Myc-activated lncRNA CCAT1 expression contribute to colon cancer tumorigenesis and the metastatic process and could predict the clinical outcome of colon cancer and be a potential target for lncRNA direct therapy.

The mammalian vomeronasal organ detects complex chemical signals that convey information about gender, strain, and the social and reproductive status of an individual. How these signals are encoded is poorly understood. We developed transgenic mice expressing the calcium indicator G-CaMP2 and analyzed population responses of vomeronasal neurons to urine from individual animals. A substantial portion of cells was activated by either male or female urine, but only a small population of cells responded exclusively to gender-specific cues shared across strains and individuals. Female cues activated more cells and were subject to more complex hormonal regulations than male cues. In contrast to gender, strain and individual information was encoded by the combinatorial activation of neurons such that urine from different individuals activated distinctive cell populations.Pheromones are a group of chemicals critical for social communication in many animal species (1,2). Information on sex, strain, social rank, reproductive status, and terrestrial ownership is represented in the complex pheromone components in urine and bodily secretions. In mice, detection of such complex chemical signals by the vomeronasal organ (VNO) and the olfactory epithelium plays an important role in triggering endocrine changes and eliciting innate territorial aggression and mating behaviors (3-5). The rodent VNO expresses more than 250 receptors that detect pheromones and transmit the signals to the brain (6-11). It is not well understood how these neurons encode information about gender and individuals. Urine contains hundreds or even thousands of substances, only a handful of which have been identified as putative pheromones (12-16). The complexity of natural pheromone signals poses a challenge to our understanding of what information is transmitted to the vomeronasal neurons (17,18).Each vomeronasal neuron expresses only one of the ∼250 estimated pheromone receptor genes (6)(7)(8)(9)19,20), and the receptor's activation elevates intracellular calcium (21). To visualize pheromone-induced activity in a large population of neurons, we generated tetO-G-CaMP2 transgenic mouse lines (22)(23)(24). When crossed to animals carrying the OMP-IRES-tTA allele (25), G-CaMP2 expression was restricted to the neurons in the olfactory system (Fig. 1, A and B, and Movie S1). Electrophysiological properties of the G-CaMP2-expressing VNO neurons, as well as their response to pheromones, were indistinguishable from those of the controls ( fig. S1). The projection patterns of the sensory neurons and the innate mating and aggressive behaviors of the G-CaMP2 mice were also indistinguishable from those of wild-type and littermate control animals (figs. S2 to S5). In VNO slices prepared from 2-to 6-month-old male or female animals, application of diluted urine elicited an increase in fluorescence in ∼30 to 40% of G-CaMP2-positive neurons, some of which showed gender-specific responses ( Fig. 1C and Movies S2 and S3). We did not observe significant differences...

In the mammalian brain, similar features of the sensory stimuli are often represented in proximity in the sensory areas. However, how chemical features are represented in the olfactory bulb has been controversial. Questions have been raised as to whether specific chemical features of the odor molecules are represented by spatially clustered olfactory glomeruli. Using a sensitive probe, we have analyzed the glomerular response to large numbers of odorants at single glomerulus resolution. Contrary to the general view, we find that the representation of chemical features is spatially distributed in the olfactory bulb with no discernible chemotopy. Moreover, odor-evoked pattern of activity does not correlate directly with odor structure in general. Despite the lack of spatial clustering or preference with respect to chemical features, some structurally related odors can be similarly represented by ensembles of spatially distributed glomeruli, providing an explanation of their perceptual similarity. Whereas there is no chemotopic organization, and the glomeruli are tuned to odors from multiple classes, we find that the glomeruli are hierarchically arranged into clusters according to their odor-tuning similarity. This tunotopic arrangement provides a framework to understand the spatial organization of the glomeruli that conforms to the organizational principle found in other sensory systems.

The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior.DOI: http://dx.doi.org/10.7554/eLife.03025.001