Long non-coding RNAs at the crossroads of inflammation, cancer and angiogenesis: Molecular mechanisms and their potential as therapeutic targets.

Long non-coding RNAs (lncRNAs), a broad class of non-protein-coding RNAs, are characterized as new regulators of gene expression at the epigenetic, transcriptional, and post-transcriptional level. Thus, lncRNAs are involved in the regulation of physiological processes and the development of human diseases and cancer by modulating proinflammatory, oncogenic and proangiogenic pathways. Inflammation, cancer and angiogenesis are interlinked through a network of signals and pathways that reinforces itself through feedback loops. Inflammation triggers vessel formation to transfer immune cells and nutrients, and consequently the new vessels enhance the supply of inflammatory cells and factors. Chronic inflammation induces oncogenic transformation and angiogenesis, induced by tumour-derived signals, support tumour growth and provide the route for distal metastasis. Here we review the implication of lncRNAs in these processes and interactions in the gastrointestinal tract, with a special focus on inflammation and cancer angiogenesis. LncRNAs, due to their highly cell-, tissue- and disease-specific expression, are attractive targets for the development of novel therapeutics with limited off-target effects and toxicity. We discuss new discoveries which highlight the value of lncRNA targeting as therapeutic applications, in gastrointestinal inflammation and cancer angiogenesis, and identify gaps in our current knowledge and understanding. We illustrate advancing approaches, their advantages and challenges for the pharmacological targeting of lncRNAs.