Long non-coding RNAs and cancer: a new frontier of translational research?

Abstract

Tiling array and novel sequencing technologies have made available the transcription profile of the entire human genome. However, the extent of transcription and the function of genetic elements that occur outside of protein-coding genes, particularly those involved in disease, are still a matter of debate. In this review, we focus on long non-coding RNAs (lncRNAs) that are involved in cancer. We define lncRNAs and present a cancer-oriented list of lncRNAs, list some tools (for example, public databases) that classify lncRNAs or that scan genome spans of interest to find whether known lncRNAs reside there, and describe some of the functions of lncRNAs and the possible genetic mechanisms that underlie lncRNA expression changes in cancer, as well as current and potential future applications of lncRNA research in the treatment of cancer.

Figure 1

LncRNA categories and functions. Several classes and functions of lncRNAs are depicted. The main function of lncRNA seems so far to regulate PCG transcription; indeed, lncRNA can either enhance or repress PCG transcription by changes in the chromatin state of the PCGs (for example, by histone methylating or acetylating). Enhancer RNAs derive from transcription of enhancer elements that can be located several kilobases upstream of target genes. Enhancer DNA can both regulate gene expression by DNA looping and direct DNA–DNA interaction with the target promoter, and they also transcribe non-polyA RNAs (that is, eRNA). The function and the role of eRNAs is at this moment unknown. Overall, both long ncRNAs (lincRNA, a-ncRNAs and AS-ncRNAs) and small ncRNAs (for example, siRNA and miRNA) regulate transcription and post transcription steps of protein synthesis, respectively. At the bottom of coding and non-coding transcription units that are shown in picture, the reader can find the peak diagram for CHIP-seq experiments concerning histone modifications: H3K4Me1, mono methylation at lysine 4 of histone 3 (often found near regulatory elements); H3K4Me3, tri methylation at lysine 4 of histone 3 (often found near promoters); H3K36Me3, tri methylation at lysine 36 of histone 3 (often found near active transcripts).