title: De-repressing LncRNA-Targeted Genes to Upregulate Gene Expression: Focus on Small Molecule Therapeutics.
abstract: Non-protein coding RNAs (ncRNAs) make up the overwhelming majority of transcripts in the genome and have recently gained attention for their complex regulatory role in cells, including the regulation of protein-coding genes. Furthermore, ncRNAs play an important role in normal development and their expression levels are dysregulated in several diseases. Recently, several long noncoding RNAs (lncRNAs) have been shown to alter the epigenetic status of genomic loci and suppress the expression of target genes. This review will present examples of such a mechanism and focus on the potential to target lncRNAs for achieving therapeutic gene upregulation by de-repressing genes that are epigenetically silenced in various diseases. Finally, the potential to target lncRNAs, through their interactions with epigenetic enzymes, using various tools, such as small molecules, viral vectors and antisense oligonucleotides, will be discussed. We suggest that small molecule modulators of a novel class of drug targets, lncRNA-protein interactions, have great potential to treat some cancers, cardiovascular disease, and neurological disorders.
authors.affiliation: 1] Department of Molecular and Cellular Pharmacology, University of Miami Miller School of Medicine, Miami, Florida, USA [2] Department of Psychiatry and Behavioral Sciences and Center for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Roya Pedram
authors.initials: RP
authors.lastname: Fatemi
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences and Center for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, Florida, USA [2] Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Velmeshev
authors.affiliation: 1] Department of Psychiatry and Behavioral Sciences and Center for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, Florida, USA [2] Department of Biochemistry and Molecular Biology, University of Miami Miller School of Medicine, Miami, Florida, USA.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Faghihi