No abstract

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.

The newly proposed variable-number tandem-repeat (VNTR) typing system, which includes a basic 15-locus set and a high-resolution 24-locus set ( Tuberculosis (TB) remains a big threat to human health, especially in developing countries. China is one of the high-burden countries in the world, with a TB incidence of 101/100,000 population and a mortality rate of 17/100,000 population (23). The emergence of multidrug-resistant Mycobacterium tuberculosis strains and coinfection with M. tuberculosis and human immunodeficiency virus make the situation even worse. In recent years, molecular typing methods have become useful tools for the control of TB and help to indicate possible epidemiological links between TB patients, detect outbreaks and laboratory cross-contamination, and distinguish exogenous reinfection from endogenous reactivation in relapse cases.In China, the most prevalent Mycobacterium tuberculosis strains belong to the Beijing family, which accounts for more than a quarter of all TB cases worldwide (2, 4). The M. tuberculosis Beijing family is a genetically homogeneous group. These strains are characterized by highly similar multiband patterns by restriction fragment length polymorphism (RFLP) analysis with IS6110 (IS6110-RFLP) and highly similar patterns by spacer oligonucleotide typing (spoligotyping) that show a lack of hybridization signals 1 to 34 and the hybridization of at least three of the spacers from signals 35 to 43 (12, 22). Therefore, spoligotyping is virtually unable to differentiate the members of the Beijing family, whereas IS6110-RFLP remains the "gold standard" method for the typing of these strains, as it has the highest discriminatory power (11-13). Unfortunately, the latter method is cumbersome and timeconsuming and requires large quantities of DNA; accordingly, simpler and more discriminatory methods are being searched for and developed.The development and application of the variable-number tandem-repeat (VNTR) method for the typing of M. tuberculosis became an important methodological achievement toward obtaining a better understanding of the molecular epidemiology of TB (19). The VNTR method is an otherwise well-known approach and technically relies on PCR amplification and calculation of the numbers of repeats on the basis of the size of the amplified product. The 12-locus mycobacterial interspersed repetitive-unit (MIRU)-VNTR scheme has been widely used (1,8,17), although it showed a limited ability to discriminate strains of the Beijing family (9,11,13,16,20). The newly proposed 15-and 24-locus systems were demonstrated to have higher discriminatory powers with a worldwide collection of M. tuberculosis strains (18) and also with members of the Beijing family of strains from Japan (6, 24).The Beijing genotype strains constitute a significant proportion of the circulating M. tuberculosis strains within large regions of the world, such as East Asia, Russia, and South Africa (2,4,12,13). The recent global dissemination of these strains is threatening TB control programs worldwide....