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Long non-coding RNAs (lncRNAs) have emerged as integral components of E2F1-regulated gene regulatory networks (GRNs), but their implication in advanced or treatment-refractory malignancy is unknown. Methods: We combined high-throughput transcriptomic approaches with bioinformatics and structure modeling to search for lncRNAs that participate in E2F1-activated prometastatic GRNs and their phenotypic targets in the highly-relevant case of E2F1-driven aggressive bladder cancer (BC). RNA immunoprecipitation was performed to verify RNA-protein interactions. Functional analyses including qRT-PCR, immunoblotting, luciferase assays and measurement of extracellular fluxes were conducted to validate expression and target gene regulation. Results: We identified E2F1-responsive lncRNA-SLC16A1-AS1 and its associated neighboring protein-coding gene, SLC16A1/MCT1, which both promote cancer invasiveness. Mechanistically, upon E2F1-mediated co-transactivation of the gene pair, SLC16A1-AS1 associates with E2F1 in a structure-dependent manner and forms an RNA-protein complex that enhances SLC16A1/MCT1 expression through binding to a composite SLC16A1-AS1:E2F1-responsive promoter element. Moreover, SLC16A1-AS1 increases aerobic glycolysis and mitochondrial respiration and fuels ATP production by fatty acid β-oxidation. These metabolic changes are accompanied by alterations in the expression of the SLC16A1-AS1:E2F1-responsive gene PPARA, a key mediator of fatty acid β-oxidation. Conclusions: Our results unveil a new gene regulatory program by which E2F1-induced lncRNA-SLC16A1-AS1 forms a complex with its transcription factor that promotes cancer metabolic reprogramming towards the acquisition of a hybrid oxidative phosphorylation/glycolysis cell phenotype favoring BC invasiveness.

Logging and forest loss continues to be a major problem within Southeast Asia and as a result, many species are becoming threatened or extinct. The present study provides the first detailed and comprehensive ecological data on the Siberut macaque (Macaca siberu), a primate species living exclusively on the island of Siberut off the west coast of Sumatra. Our results show that M. siberu is ecologically similar to its closest relative M. nemestrina occurring on the mainland, both species being semi-terrestrial, mainly frugivorous (75-76%), exhibit a large daily travel distance for their group size and spend more time on traveling than any other macaque species. The habitat of Siberut macaques was floristically very diverse (Simpson’s index D=0.97), although somewhat impoverished in tree species richness, and had a lower tree basal area and a lower rattan density compared to other forests in Malesia (both rattan and palm tree fruit being an important food resource for Macaca siberu due to their long fruiting periods). These factors may lead to a lower diversity and abundance of fruit resources, and coupled with a high degree of frugivory of Siberut macaques, may explain the large amount of traveling observed in this species. The large home range requirements and strong dependence on fruit are important factors that need to be considered when developing conservation measures for this IUCN-listed (Category Vulnerable) species.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-137) contains supplementary material, which is available to authorized users.

Macaque social relationships differ greatly between species. Based on captive studies that focus mainly on females, researchers have classified stumptail macaque (Macaca arctoides) social relationships as tolerant, as indicated by a high rate of affiliation, frequent aggression, and symmetrical conflicts. To accumulate more data on male social relationships, which are relatively understudied, and to generate comparative data, we investigated male social relationships in a provisioned group of 68 free-ranging, naturally dispersing stumptail macaques in southern Thailand. We collected continuous focal animal and ad libitum data on 7 adult and 2 subadult males, recording social behavior during 283 contact hours between December 2006 and March 2007. Stumptail macaques of this population were less tolerant than predicted based on previous studies on captive groups: Rates of spatial proximity, affiliation, and aggression were low, most males directed affiliative behavior toward higher-ranking males, and conflicts were generally of low intensity and relatively asymmetrical. Thus, male stumptail macaques of the focal group appear to differ in their social style from a previous study of a captive group that Int J Primatol (2009) mainly comprised of females. In some traits, they are even more intolerant than rhesus macaques, an intensively studied intolerant macaque species. We also compare our data on stumptail macaque males to those on other male macaques, but available data are too sparse to draw final conclusions.