The functional role of long non-coding RNA in human carcinomas - PubMed (original) (raw)

Review

The functional role of long non-coding RNA in human carcinomas

Ewan A Gibb et al. Mol Cancer. 2011.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as new players in the cancer paradigm demonstrating potential roles in both oncogenic and tumor suppressive pathways. These novel genes are frequently aberrantly expressed in a variety of human cancers, however the biological functions of the vast majority remain unknown. Recently, evidence has begun to accumulate describing the molecular mechanisms by which these RNA species function, providing insight into the functional roles they may play in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in human cancer.

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Figures

Figure 1

Figure 1

Publications describing cancer-associated ncRNAs. Entries are based on a National Library of Medicine Pubmed search using the terms "ncRNA" or "non-coding RNA" or "noncoding RNA" or non-protein-coding RNA" with cancer and annual (Jan.1-Dec.31) date limitations.

Figure 2

Figure 2

Timeline of cancer-associated ncRNA discoveries relative to transcriptome analysis technologies (not drawn to scale).

Figure 3

Figure 3

Proposed mechanism of HOTAIR mediated gene silencing of 40 kb of the HOXD locus, which is involved in developmental patterning. The HOTAIR lncRNA is transcribed from the HOXC locus and functions in the binding and recruitment and binding of the PRC2 and LSD1 complex to the HOXD locus. For clarity, only the PRC2 complex is indicated in the above figure. Through an undetermined mechanism, the _HOTAIR_-PRC2-LSD1 complex is redirected to the HOXD locus on chromosome 2 where genes involved in metastasis suppression are silenced through H3K27 methylation and H3K4 demethylation. This drives breast cancer cells to develop gene expression patterns that more closely resemble embryonic fibroblasts than epithelial cells.

Figure 4

Figure 4

Expression and processing of MALAT1 transcripts. Full length 7.5 kb MALAT1 RNA is processed by RNaseP and RNaseZ to generate the small ncRNA mascRNA, which is then exported to the cytoplasm. The larger MALAT1 RNA is retained in the nuclear speckles where it is thought to have a role in regulating alternative splicing machinery.

Figure 5

Figure 5

Proposed mechanism of HULC upregulation in hepatocellular carcinoma. (1) The kinase PRKACB functions as an activator of CREB. (2) Phosphorylated (activated) CREB forms part of the RNA pol II transcriptional machinery to activate HULC expression. (3) Abundant HULC RNA acts as a molecular sponge to sequester and inactivate the repressive function miR-372. (4) PRKACB levels increase, as transcripts are normally translationally repressed by high miR-372 levels.

Figure 6

Figure 6

Genomic locations of the five classes of T-UCRs. The exons of coding genes are indicated by boxes, while the locations of the T-UCR elements are marked by a double-T bar. The five possible positions are as indicated exonic, partly exonic, exon containing, intronic and intergenic.

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