Long noncoding RNAs in development and cancer: potential biomarkers and therapeutic targets

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Abstract

Long noncoding RNAs are emerging as key players in various fundamental biological processes. We highlight the varied molecular mechanisms by which lncRNAs modulate gene expression in diverse cellular contexts and their role in early mammalian development in this review. Furthermore, it is being increasingly recognized that altered expression of lncRNAs is specifically associated with tumorigenesis, tumor progression and metastasis. We discuss various lncRNAs implicated in different cancer types with a focus on their clinical applications as potential biomarkers and therapeutic targets in the pathology of diverse cancers.

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Long noncoding RNA as modular scaffold of histone modification complexes.

Miao-Chih Tsai, Ohad Manor, Yue Wan … (2010)

Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.

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RNA maps reveal new RNA classes and a possible function for pervasive transcription.

Philipp Kapranov, Jill Cheng, Sujit Dike … (2007)

Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.

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A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

Laura Poliseno, Leonardo Salmena, JiangWen Zhang … (2010)

The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.

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Author and article information

Contributors

Roshan Fatima: roshanfb@jncasr.ac.in

Vijay Suresh Akhade: vijayakhade@jncasr.ac.in

Debosree Pal: debosreep@jncasr.ac.in

Satyanarayana MR Rao: mrsrao@jncasr.ac.in

Journal

Journal ID (nlm-ta): Mol Cell Ther

Journal ID (iso-abbrev): Mol Cell Ther

Title: Molecular and cellular therapies

Publisher: BioMed Central (London )

ISSN (Electronic): 2052-8426

Publication date (Electronic): 12 June 2015

Publication date PMC-release: 12 June 2015

Publication date Collection: 2015

Volume: 3

Electronic Location Identifier: 5

Affiliations

Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Jakkur, Bangalore 560064 India

Article

Publisher ID: 42

DOI: 10.1186/s40591-015-0042-6

PMC ID: 4469312

PubMed ID: 26082843

SO-VID: e745f3ff-c118-4504-aec1-82a1a8b9e4fe

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.