Abstract
Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being “transcriptional noise”, increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.
Highlights
Hepatocellular carcinoma (HCC) is one of the several malignancies in which mortality has been increasing, in particular, in Western populations [1]
Despite the diverse features that are displayed by long non-coding RNAs (lncRNAs), as a general rule, they are broadly classified according to their biogenesis and genomic positions in relation to protein-coding genes, lncRNAs can be broadly classified into: (i) antisense RNAs or natural antisense transcripts (NATs); (ii) bidirectional RNAs; (iii) long intergenic RNAs; and (iv) sense intronic RNAs [12,38,39] (Figure 1)
It has been shown that lncRNA-ATB can promote the invasion-metastasis cascade, either by inducing epithelial-tomesenchymal transition (EMT) through the upregulation of ZEB1 and ZEB2 or by binding IL-11 mRNA and triggering STAT3 signaling [170]. These findings suggest that lncRNA-ATB predisposes HCC patients to metastasis and may potentially serve as a target for anti-metastatic therapies
Summary
Hepatocellular carcinoma (HCC) is one of the several malignancies in which mortality has been increasing, in particular, in Western populations [1]. LncRNAs interact with transcription factors and may variably guide them to [14] or prevent them from binding to their target genes [15] They may act as enhancers by rearranging chromatin or may act as sponges to bind proteins or microRNAs [16,17,18,19]. Of their many roles, the best described is the recruitment of chromatin modifying complexes to specific genomic regions [6,11,13,20,21,22,23] via chromosomal looping [24,25]. We will further provide an overview of the latest studies that are aimed at elucidating the potential uses of lncRNAs as diagnostic/prognostic markers and as therapeutic targets in HCC
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