given ceRNA must be large enough to relieve or overcome miRNA binding and
suppression of competing transcripts; (2) transcripts sharing MREs for multiple
miRNAs will form more robust ceRNA networks; and (3) since few transcripts
among all those that are bound by any given miRNA are primary targets for
suppression, some MREs of any given ceRNA may be more influential than others
in its ceRNA network [34].
3 lncRNA and Epigenetic Deregulation in Cancer
Many innovations in non-coding RNA research have been spurred on by the
persistent need to better understand the molecular underpinnings of human diseases.
Cancer studies in particular have contributed greatly to our overall understanding
of the interface between epigenetics and lncRNA. Several lncRNAs have been
comprehensively established as playing oncogenic roles in many kinds of tumour,
whereas others have emerged as tumour suppressor lncRNAs. In this section, we
highlight several interesting insights into the roles of lncRNAs associated with
epigenetic regulation in promoting or preventing cancer, how they influence tumour
responses to anticancer therapies and how some of these lncRNAs themselves
can be exploited as biomarkers or therapeutic targets in cancer (Table 1).
3.1 Oncogenic lncRNAs: HOTAIR, MALAT1, TUG1
and MIAT
HOTAIR was one of the first lncRNAs to be linked to cancer progression, and
it remains one of the best-studied oncogenic lncRNAs. HOTAIR overexpression
promotes lung cancer metastasis both in vitro and in vivo, and it has also been
demonstrated that HOTAIR overexpression can “re-target” PRC2 to repress over
800 genes, including known breast cancer tumour suppressors, and that the oncogenic effect of HOTAIR this context is co-dependent on PRC2 [35]. Furthermore,
HOTAIR has been implicated in c-Myc transcriptional activation mechanisms in
breast cancer, contributing to breast cancer growth and progression in both in vitro
and in vivo models. Therefore, HOTAIR does not exclusively mediate transcriptional silencing but can also coordinate transcriptional activation in breast cancer
MALAT1 which earned its name when it was found overexpressed in non-small-cell
lung cancer (NSCLC) metastases. It was one of the first long non-coding transcripts
found to be relevant in cancer [36]. A landmark MALAT1 knockout study of
NSCLC demonstrated that MALAT1 significantly alters the expression levels of
metastasis-associated genes in NSCLC cells but does not cause significant mRNA
splicing changes [37]. MALAT1 was also shown to be required for lung cancer
metastasis of xenograft NSCLC tumours in mice both by MALAT1 gene knockout
Altered Long Non-coding RNA Expression in Cancer: Potential Biomarkers. . .
409
suppression of competing transcripts; (2) transcripts sharing MREs for multiple
miRNAs will form more robust ceRNA networks; and (3) since few transcripts
among all those that are bound by any given miRNA are primary targets for
suppression, some MREs of any given ceRNA may be more influential than others
in its ceRNA network [34].
3 lncRNA and Epigenetic Deregulation in Cancer
Many innovations in non-coding RNA research have been spurred on by the
persistent need to better understand the molecular underpinnings of human diseases.
Cancer studies in particular have contributed greatly to our overall understanding
of the interface between epigenetics and lncRNA. Several lncRNAs have been
comprehensively established as playing oncogenic roles in many kinds of tumour,
whereas others have emerged as tumour suppressor lncRNAs. In this section, we
highlight several interesting insights into the roles of lncRNAs associated with
epigenetic regulation in promoting or preventing cancer, how they influence tumour
responses to anticancer therapies and how some of these lncRNAs themselves
can be exploited as biomarkers or therapeutic targets in cancer (Table 1).
3.1 Oncogenic lncRNAs: HOTAIR, MALAT1, TUG1
and MIAT
HOTAIR was one of the first lncRNAs to be linked to cancer progression, and
it remains one of the best-studied oncogenic lncRNAs. HOTAIR overexpression
promotes lung cancer metastasis both in vitro and in vivo, and it has also been
demonstrated that HOTAIR overexpression can “re-target” PRC2 to repress over
800 genes, including known breast cancer tumour suppressors, and that the oncogenic effect of HOTAIR this context is co-dependent on PRC2 [35]. Furthermore,
HOTAIR has been implicated in c-Myc transcriptional activation mechanisms in
breast cancer, contributing to breast cancer growth and progression in both in vitro
and in vivo models. Therefore, HOTAIR does not exclusively mediate transcriptional silencing but can also coordinate transcriptional activation in breast cancer
MALAT1 which earned its name when it was found overexpressed in non-small-cell
lung cancer (NSCLC) metastases. It was one of the first long non-coding transcripts
found to be relevant in cancer [36]. A landmark MALAT1 knockout study of
NSCLC demonstrated that MALAT1 significantly alters the expression levels of
metastasis-associated genes in NSCLC cells but does not cause significant mRNA
splicing changes [37]. MALAT1 was also shown to be required for lung cancer
metastasis of xenograft NSCLC tumours in mice both by MALAT1 gene knockout
Altered Long Non-coding RNA Expression in Cancer: Potential Biomarkers. . .
409