MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches - PubMed (original) (raw)

Review

MALAT1: a druggable long non-coding RNA for targeted anti-cancer approaches

Nicola Amodio et al. J Hematol Oncol. 2018.

Abstract

The deeper understanding of non-coding RNAs has recently changed the dogma of molecular biology assuming protein-coding genes as unique functional biological effectors, while non-coding genes as junk material of doubtful significance. In the last decade, an exciting boom of experimental research has brought to light the pivotal biological functions of long non-coding RNAs (lncRNAs), representing more than the half of the whole non-coding transcriptome, along with their dysregulation in many diseases, including cancer.In this review, we summarize the emerging insights on lncRNA expression and functional role in cancer, focusing on the evolutionary conserved and abundantly expressed metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) that currently represents the best characterized lncRNA. Altogether, literature data indicate aberrant expression and dysregulated activity of MALAT1 in human malignancies and envision MALAT1 targeting as a novel treatment strategy against cancer.

Keywords: Epigenetics; Experimental therapeutics; Long non-coding RNA; MALAT1; Non-coding RNA; lncRNA.

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The authors declare that they have no competing interests.

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Figures

Fig. 1

Fig. 1

Mechanisms of MALAT1 regulation. MALAT1 expression can be positively or negatively affected by transcription factors, epigenetic changes (histone or CpG methylation/demethylation), miRNAs and binding proteins stabilizing the triple helix, such as METTL16

Fig. 2

Fig. 2

MALAT1 functions in human cancer. a: MALAT1 can affect mRNA transcription by regulating splicing of pre-mRNAs through interacting with and regulating phosphorylation of serine- and arginine-rich (SR) proteins into nuclear speckles. b: MALAT1 interacts with PRC2 components EZH2, SUZ12, and EED and reduces target gene or miRNA expression by promoting trimethylation of histone H3 at lysine 27 (H3K27me3). c: MALAT1 can affect mRNA transcription by facilitating transcription factor (TF) binding to promoter of target genes. d: MALAT1 can sequestrate miRNAs acting as a sponge, thus activating the expression of miRNA targets

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