Human endogenous retroviruses (HERVs) play pivotal roles in the development of breast cancer. However, the detailed mechanisms of noncoding HERVs remain elusive. Here, our genome-wide transcriptome analysis of HERVs revealed that a primate long noncoding RNA, which we dubbed TROJAN, was highly expressed in human triple-negative breast cancer (TNBC). TROJAN promoted TNBC proliferation and invasion and indicated poor patient outcomes. We further confirmed that TROJAN could bind to ZMYND8, a metastasis-repressing factor, and increase its degradation through the ubiquitin-proteasome pathway by repelling ZNF592. TROJAN also epigenetically up-regulated metastasis-related genes in multiple cell lines. Correlations between TROJAN and ZMYND8 were subsequently confirmed in clinical samples. Furthermore, our study verified that antisense oligonucleotide therapy targeting TROJAN substantially suppressed TNBC progression in vivo. In conclusion, the long noncoding RNA TROJAN promotes TNBC progression and serves as a potential therapeutic target.

BackgroundRecent anti-malarial resistance monitoring in Angola has shown efficacy of artemether–lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013.MethodsDuring January–June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate–amodiaquine (ASAQ), or dihydroartemisinin–piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1).ResultsA total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91–100) for AL in Benguela, 99.9% (95–100) for ASAQ in Benguela, 88.1% (81–95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96–100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility.ConclusionsNo evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1712-4) contains supplementary material, which is available to authorized users.

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This study examined the relationship between social support (Social Provisions Scale) and stress (Perceived Stress Scale) in a sample of male firefighters in a midwestern community (N ϭ 53). The authors assessed 5 types of perceived support from 2 sources: peer firefighters and supervisors. Results indicate that reassurance of worth and social integration support from supervisors had the strongest negative association with stress. The study critically examined the "unidirectional linear" assumption that a unit increase in support corresponds to a unit increase in adjustment throughout the full range of support scores. Reassurance of worth support from peers exhibited a curvilinear pattern of threshold effects. For individuals with the lowest levels of support, there was a strong negative association between perceived support and stress, but for firefighters above the median, the association was not significant.