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Computational Molecular Biology 2015, Vol. 5, No. 2, 1-4
http://cmb.biopublisher.ca
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lncRNAs related to infiltration and metastasis in
breast cancer
More and more studies show that a part of lncRNAs
play an important role during process of infiltration
and metastasis in breast cancer. HOTAIR, a 2.2Kb
carcinogenic LncRNA, located in the HOXC locus, is
transcribed in an antisense orientation from the HOXC
locus, which could promote metastasis by changing
state of chromatin. In breast cancer, HOTAIR
expression is upregulated in both primary and
metastatic tumors, and its expression in primary
tumors is strongly correlated with later metastasis,
poor prognosis, and even death. HOTAIR acts in trans
as a repressor of the HOXD locus by recruiting PRC2,
leading to trimethylation of H3K27 and subsequent
transcriptional silencing, and then promotes invasion
and metastasis of breast cancer by facilitating a series
of target proteins. Recently research shows that the
promoter of HOTAIR contains multiple functional
estrogen response elements near the transcription start
site, and is transcriptionally induced by estrogen, this
may contribute to illuminating correlation between
development of breast cancer and HOTAIR
upregulated (Bhan A, et al., 2013). Steroid receptor
RNA activator 1(SRA 1), a type of 0.87Kb secondary
structural lncRNA, was firstly obtained from
experiment (Novikova IV, et al., 2012).Several
research data show that SRA-1 energetically involves
in glucose uptake, signaling transduction, production
of T3 and metastasis (Shore A N, et al., 2012). SRA-1
may be involved in carcinogenesis of sexual hormone
through regulating steroid receptor and expressive
levels of other transcription factor. Metastasis
associated lung adenocarcinoma transcript 1
（
MALAT-1) is an intergenic lncRNA, which was
firstly discovered in non-small cell lung cancer as a
prognostic marker of later development or metastasis
(Gutschner T, et al., 2013). MALAT-1 expression is
typically upregulated in breast cancer and
metastasizing tissues and has been associated with
invasion and metastasis of breast cancer.
lncRNAs involved in epigenetic regulation of breast
cancer
Epigenetics refers to the study of mechanisms that
alter gene expression without altering the primary
DNA sequence, and it is mainly composed of DNA
methylation, histone deacetylase, genomic imprinting
and random inactivation of chromosome. DNA
methylation, an important component of epigenetics,
is essential to protecting DNA from incising by
enzyme. DNA methyltransferase (DNMT) may affect
expression of some genes by methylation modification
at promoter. Such as in breast cancer tissue,
methyltransferase modifies genic promoter of MEG3,
thus, leads to downregulaion of MEG3.Histone
modification is also a crucial way of epigenetics
(Wenzhu Lou, et al., 2011). Genomic imprinting
results from differential epigenetic modifications
(such as DNA methylation and histone modifications)
established separately in the maternal and paternal
germ lines, respectively, such as H19 performed in
breast cancer. Some lncRNAs affect genetic coding by
changing expressive levels without altering genetic
sequence of them, and such a mechanism is confirmed
to regulating characteristics of epigenetics (Orom U A,
et al., 2011).
Significance of lncRNAs contributed to diagnosis
and therapy of breast cancer
The main purpose of tumor research is to find
sensitive and specific markers for carcinoma, thus to
provide significant values for early diagnosis and
therapy, and assement of prognosis of malignant.
Researchers found, so far, that a part of lncRNAs that
expressed in tumors own high sensitivity and
specificity, and they have potential value of becoming
new markers for cancers. At present, researchers have
already found some LncRNAs play an important role
in breast cancer, for example serving as a biological
marker, to predict stages, metastasis and survival rate
of breast cancer patient. The expression amount of
HOTAIR in a third of primary breast cancer is defined
as 125 fold more than that detected in normal breast
epithelia, and 2000 fold in metastatic tissues. It is
generally accepted that HOTAIR has become an
independent clinical risk factors. In addition, BC200
、
XIST
、
MALAT-1
、
BC1 are abnormally expressed in
breast cancer, and these lncRNAs will provide new
ideas for diagnosis and therapy of breast cancer.
LncRNAs research has become a new hotspot in the
field of modern molecular biology though our