Emerging roles of long non-coding RNA in cancer

Abstract

Since comprehensive analysis of the mammalian genome revealed that the majority of genomic products are transcribed in long non-coding RNA (lncRNA), increasing attention has been paid to these transcripts. The applied next-generation sequencing technologies have provided accumulating evidence of dysregulated lncRNA in cancer. The implication of this finding can be seen in many forms and at multiple levels. With impacts ranging from integrating chromatin remodeling complexes to regulating transcription and post-transcriptional processes, aberrant expression of lncRNA may have repercussions in cell proliferation, tumor progression or metastasis. lncRNA may act as enhancers, scaffolds or decoys by physically interacting with other RNA species or proteins, resulting in a direct impact on cell signaling cascades. Even though their functional classification is well-established in the context of cancer, clearer characterization in terms of their phenotypic outputs is needed to optimize and identify suitable candidates that enable the development of new therapeutic strategies and the design of novel diagnostic approaches. The present article aims to outline different cancer-associated lncRNA according to their contribution to tumor suppression or tumor promotion based on their most current functional annotations.

Keywords: epithelial-to-mesenchymal transition; long non-coding RNA; tumor drivers; tumor plasticity; tumor suppressors.

Figure 1

Long non‐coding RNA (lncRNA) and the p53network. A, LED is transcriptionally induced by p53 and epigenetically stimulates the production of eRNA (enhancer RNA) by the acetylation of histone H3K9 on the p53‐bound enhancer regions (p53BER). B, Transactivation of p53‐target genes is activated by means of direct binding between p53 and lncRNA MEG3. C, LincRNA‐p21 is transcribed by p53. Next, LincRNA‐p21 forms the repressive complex together with the ribonucleoprotein Hnrnpk to suppress survival‐related genes. D, Transcriptional divergence of p53 resulting in the transcription of DINO, which, in turn, may activate p53 transcription. Physical interaction of DINO and p53 induces p53‐target genes

Figure 2

Long non‐coding RNA (lncRNA) involved in tumor plasticity. Aberrantly expressed lncRNA may have an important impact in the EMT‐MET processes by interacting with diverse signaling cascades