Molecular and Cellular Mechanisms of Action of Tumour Suppressor GAS5 LncRNA - PubMed (original) (raw)

Review

Molecular and Cellular Mechanisms of Action of Tumour Suppressor GAS5 LncRNA

Mark R Pickard et al. Genes (Basel). 2015.

Abstract

It is increasingly recognised that lncRNAs play essential regulatory roles in fundamental biological processes and, consequently, that their dysregulation may contribute to major human diseases, including cancer. Better understanding of lncRNA biology may therefore offer new insights into pathogenetic mechanisms and thereby offer novel opportunities for diagnosis and therapy. Of particular interest in this regard is GAS5 lncRNA, which is down-regulated in multiple cancers, with expression levels related to both clinico-pathological characteristics and patient prognosis. Functional studies have further shown that GAS5 lncRNA both inhibits the proliferation and promotes the apoptosis of multiple cell types, and that together these cellular mechanisms of action are likely to form the basis of its tumour suppressor action. At the same time, advances have been made in our understanding of the molecular mechanisms of GAS5 lncRNA action in recent years, including riborepression of certain steroid hormone receptors and sequestration of miR-21, impacting key regulatory pathways of cell survival. Overall this accumulating knowledge has the potential to improve both the diagnosis and treatment of cancer, and ultimately patient outcome.

Keywords: GAS5; apoptosis; cancer; cell proliferation; lncRNA; tumour suppressor.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Genomic context, gene structure and selected products of the human GAS5 gene. For genomic context, HUGO Gene Nomenclature Committee (HGNC) approved gene symbols are used, with the corresponding HGNC identity number given below each symbol. Exon/intron structure is based on published data [6]; note the presence of two alternative 5′-splice donor sites in exon 7. The two possible resulting mature lncRNAs are termed GAS5b (contains exon 7b and corresponds to the GAS5 reference sequence, NR_002578.2) and GAS5a (contains exon 7a); the latter is predicted to be 39 bases shorter than GAS5a (based on [6] and GenBank: AF141346.1). The additional GAS5 expressed sequence tags (ESTs) shown here have all been reported to induce growth arrest in lymphoid cell lines [10].

Figure 2

Figure 2

Interplay between mammalian target of rapamycin (mTOR) and nonsense-mediated decay (NMD) regulates cellular GAS5 lncRNA levels.

Figure 3

Figure 3

Summary of biological processes that are regulated by GAS5 lncRNA, including possible downstream molecular targets. ↓ and ↑ = down- and up-regulation, respectively.

Similar articles

Cited by

References

    1. Kung J.T., Colognori D., Lee J.T. Long noncoding RNAs: Past, present, and future. Genetics. 2013;193:651–669. doi: 10.1534/genetics.112.146704. - DOI - PMC - PubMed
    1. Morris K.V., Mattick J.S. The rise of regulatory RNA. Nat. Rev. Genet. 2014;15:423–437. doi: 10.1038/nrg3722. - DOI - PMC - PubMed
    1. Wapinski O., Chang H.Y. Long noncoding RNAs and human disease. Trends Cell Biol. 2011;21:354–361. doi: 10.1016/j.tcb.2011.04.001. - DOI - PubMed
    1. Hrdlickova B., de Almeida R.C., Borek Z., Withoff S. Genetic variation in the non-coding genome: Involvement of micro-RNAs and long non-coding RNAs in disease. Biochim. Biophys. Acta. 2014;1842:1910–1922. doi: 10.1016/j.bbadis.2014.03.011. - DOI - PubMed
    1. Schneider C., King R.M., Philipson L.A.B. Genes specifically expressed at growth arrest of mammalian cells. Cell. 1988;54:787–793. doi: 10.1016/S0092-8674(88)91065-3. - DOI - PubMed

Publication types

LinkOut - more resources