Long noncoding RNAs in cancer: from function to translation

Abstract

While our understanding of the molecular mechanisms underlying cancer has significantly improved, most of our knowledge focuses on protein-coding genes that make up a fraction of the genome. Recent studies have uncovered thousands of long noncoding RNAs (lncRNAs) that populate the cancer genome. A subset of these molecules shows striking cancer- and lineage-specific expression patterns, suggesting they may be potential drivers of cancer biology and have utility as clinical biomarkers. Here, we discuss emerging modalities of lncRNA biology and their interplay with cancer-associated concepts, including epigenetic regulation, DNA damage and cell cycle control, microRNA silencing, signal transduction pathways, and hormone-driven disease. Additionally, we highlight the translational impact of lncRNAs, tools for their mechanistic investigation, and directions for future lncRNA research.

Figure 1. LncRNAs play a crucial role within major areas of cancer progression and metastasis

Long noncoding RNA (lncRNAs) mediate several cancer-associated processes, including epigenetic regulation, DNA damage and cell cycle control, microRNA (miRNA) silencing, signal transduction pathways, and hormone-driven disease.

Figure 2. Translational implications of lncRNAs

Long noncoding RNAs (lncRNAs) are emerging as both diagnostic and prognostic biomarkers that can be detected in tissue, serum, and urine. Antisense oligonucleotides (ASOs) can be used to directly target lncRNAs and are a promising therapeutic strategy in cancer.

Figure 3. Tools for lncRNA investigation

Emerging areas for investigation in the long noncoding RNA (lncRNA) field include improved discovery methods, unbiased interactome analysis, transcript visualization and localization, RNA structure determination, discovery of small peptides produced from short open reading frames (sORF), and identification and comprehension of lncRNA variants.