Efficient Protein Transfection by Swarms of Chemically Powered Plasmonic Virus-Sized Nanorobots.

Transfection is based on nonviral delivery of nucleic acids or proteins into cells. Viral approaches are being used; nevertheless, their translational capacity is nowadays decreasing due to persistent fear of their safety, therefore creating space for the field of nanotechnology. However, nanomedical approaches introducing static nanoparticles for the delivery of biologically active molecules are very likely to be overshadowed by the vast potential of nanorobotics. We hereby present a rapid nonviral transfection of protein into a difficult-to-transfect prostate cancer cell line facilitated by chemically powered rectangular virus-sized (68 nm × 33 nm) nanorobots. The enhanced diffusion of these biocompatible nanorobots is the key to their fast internalization into cells, happening in a matter of minutes and being up to 6-fold more efficient compared to static nanorobots in a nonfueled environment. The Au/Ag plasmonic nature of these nanorobots makes them simply traceable and allows for their detailed subcellular localization. Protein transfection mediated by such nanorobots is an important step forward, challenging the field of nanomedicine and having potential in future translational medical research.

Reactivation of endogenous retroviral elements via treatment with DNMT- and HDAC-inhibitors.

Inhibitors of DNA methyltransferases (DNMTis) or histone deacetylases (HDACis) are epigenetic drugs which are investigated since decades. Several have been approved and are applied in the treatment of hematopoietic and lymphatic malignancies, although their mode of action has not been fully understood. Two recent findings improved mechanistic insights: i) activation of human endogenous retroviral elements (HERVs) with concomitant synthesis of double-stranded RNAs (dsRNAs), and ii) massive activation of promoters from long terminal repeats (LTRs) which originated from past HERV invasions. These dsRNAs activate an antiviral response pathway followed by apoptosis. LTR promoter activation leads to synthesis of non-annotated transcripts potentially encoding novel or cryptic proteins. Here, we discuss the current knowledge of the molecular effects exerted by epigenetic drugs with a focus on DNMTis and HDACis. We highlight the role in LTR activation and provide novel data from both in vitro and in vivo epigenetic drug treatment.

Erratum: DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats.

This corrects the article DOI: 10.1038/ng.3889.

DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats.

Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigenomic consequences. By mapping global transcription start site (TSS) and chromatin dynamics, we observed the cryptic transcription of thousands of treatment-induced non-annotated TSSs (TINATs) following DNMTi and HDACi treatment. The resulting transcripts frequently splice into protein-coding exons and encode truncated or chimeric ORFs translated into products with predicted abnormal or immunogenic functions. TINAT transcription after DNMTi treatment coincided with DNA hypomethylation and gain of classical promoter histone marks, while HDACi specifically induced a subset of TINATs in association with H2AK9ac, H3K14ac, and H3K23ac. Despite this mechanistic difference, both inhibitors convergently induced transcription from identical sites, as we found TINATs to be encoded in solitary long terminal repeats of the ERV9/LTR12 family, which are epigenetically repressed in virtually all normal cells.

Zinc and Copper Homeostasis in Head and Neck Cancer: Review and Meta-Analysis.

Metals are known for playing essential roles in human physiology. Copper and zinc are trace elements closely dependent on one another and are involved in cell proliferation, growth, gene expression, apoptosis and other processes. Their homeostasis is crucial and tightly controlled by a resourceful system of transporters and transport proteins which deliver copper and zinc ions to their target sites. Abnormal zinc and copper homeostasis can be seen in a number of malignancies and also in head and neck cancer. Imbalance in this homeostasis is observed as an elevation or decrease of copper and zinc ions in serum or tissue levels in patients with cancer. In head and neck cancer these altered levels stand out from those of other malignancies which makes them an object of interest and therefore zinc and copper ions might be a good target for further research of head and neck cancer development and progression. This review aims to summarize the physiological roles of copper and zinc, its binding and transport mechanisms, and based on those, its role in head and neck cancer. To provide stronger evidence, dysregulation of levels is analysed by a meta-analytical approach.