lncRNA involvement in cancer stem cell function and epithelial-mesenchymal transitions.

Epithelial to mesenchymal transition (EMT) is a cellular process in which cells composing epithelial tissue lose requirements for physical contact with neighboring cells and acquire mesenchymal characteristics consisting of increased migratory and invasive behaviors. EMT is a fundamental process that is required for initial and later events during embryogenesis. Cancer stem cells (CSCs) possess multipotency sufficient for their differentiation into bulk tumor cells and also have the capacity to undergo EMT. When CSCs initiate EMT programs the resulting cancerous mesenchymal cells become invasive and this migratory behavior also poises them for metastatic activity. Long noncoding RNAs (lncRNAs) are functional RNA molecules that do not encode proteins, yet regulate the expression of protein-coding genes through recruitment or sequestration of gene-regulatory proteins and microRNAs. lncRNA exhibit tissue-specific patterns of gene expression during development and specific sets of lncRNAs are also involved in various cancer types. This review considers the interplay between lncRNAs and the biogenesis of CSCs. We also review function of lncRNAs in EMT in CSCs. In addition, we discuss the utility of lncRNAs as biomarkers of cancer progression, and their potential use as therapeutic targets for treatment of cancer.

Nephrotoxicity of marketed antisense oligonucleotide drugs.

The field of antisense oligonucleotide (ASO)-based therapies have been making strides in precision medicine due to their potent therapeutic application. Early successes in treating some genetic diseases are now attributed to an emerging class of antisense drugs. After two decades, the US Food and Drug Administration (FDA) has approved a considerable number of ASO drugs, primarily to treat rare diseases with optimal therapeutic outcomes. However, safety is one of the biggest challenges to the therapeutic utility of ASO drugs. Due to patients' and health care practitioners' urgent demands for medicines for untreatable conditions, many ASO drugs have been approved. However, a complete understanding of the mechanisms of adverse drug reactions (ADRs) and toxicities of ASOs still need to be resolved. The range of ADRs is unique to a specific drug, while few ADRs are common to a section of drugs as a whole. Nephrotoxicity is an important concern that needs to be addressed considering the clinical translation of any drug candidates ranging from small molecules to ASO-based drugs. This article encompasses what is known about the nephrotoxicity of ASO drugs, the potential mechanisms of action(s), and recommendations for future investigations on the safety of ASO drugs.