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Computational Molecular Biology 2015, Vol. 5, No. 2, 1-4
http://cmb.biopublisher.ca
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LncRNAs are mainly transcribed by RNA polymerase
II, and they are divided into two classes of oncogenes
and tumor suppressor genes according to their functions
on the occurrence and development of cancer. These
two groups of genes, normally, can level off by
repairing DNA injuries timely or promoting abnormal
cells apoptosis, while the balance including quantity
and function could be disequilibrated by oncogenes,
and lead to cancerization finally (Jie Lv, et al., 2014).
LncRNAs are expressed in various tissues, and their
functions are diversified: interfering the expression of
downstream gene and the cutting of mRNA, combining
with DNA or proteins directly, thus to affect the
transcriptional level of genes and activity of proteins.
Thus, lncRNAs also play an important role on
epigenetic. In a word, the regulatory mechanisms of
lncRNAs are complex.
lncRNAs and breast cancer
Abnormal expression of lncRNAs in breast cancer
One of the main functions of lncRNAs is to
influencing expressive levels of downstream or other
genes through expressive changes of lncRNAs
itself.H19 is derived from a large imprinted locus on
human chromosome 11p15.5.This lncRNA is
abundantly expressed in the developing embryo,
highly expressed in the mammary bud and adjacent
tissues and differentially regulated during mammary
gland development. H19 is expressed exclusively
from the maternal allele where it acts to regulate the
expression of IGF-2 (insulin-like growth factor 2,
Igf-2), while not expressed in adult tissues (DeBaun
M R, et al., 2002). The variation of expression
quantity of H19 correlates with the development of
tumors such as cell proliferation, migration and
preterminal differentiation. These results are in favor
of the standpoint that H19 could be regarded as
oncogene. We notice that the lack of H19 would
accelerate the growth of tumors from studies of some
tumor cell lines, this finding may illerstrate the
opposite function of H19-cancer suppressor gene.
Therefore, H19 may play dual roles of promoting and
restraining cancers. LncRNA BC200 expression is
highly elevated in breast invasive tumors but not in
normal breast tissues or benign tumors. In addition,
large scale of genomic studies show that statistical
differences exist in the expression of Loc554202,
XIST, MALAT-1 and BC1 between breast cancer and
normal tissues. Long stress induced non-coding
transcript 5 (LSINCT5) is a nuclear localized lncRNA
that was discovered in screens to identify lncRNAs
upregulated upon treatment with stress inducing
chemicals, and expression of LSINCT5 is increased in
breast and ovarian cancer (Silva J M, et al., 2011).
Because of its high expression in proliferative tissues
and cancer, LSINCT5 could potentially function as a
regulator of proliferation. Additionally, knockdown
of LSINCT5 leads to altered expression of several
genes, including suppression of CXCR4, a breast
cancer marker associated with metastasis, it is
speculated that carcinogenesis of LSINCT5 could be
exerted by regulating downstream target gene and
promoting cell proliferation.
LncRNAs related to apoptosis of breast cancer
As it is now generally accepted that apoptosis plays an
essential role in oncogenesis, especially dysregulation
of some lncRNAs controlling apoptosis. We have
found that, some lncRNAs participate in the
occurrence of breast cancer through affecting
apoptosis. Growth arrest–specific 5(Gas5), a
non-protein-coding RNA, have been identified as
critical to the control of mammalian apoptosis and cell
population growth, and it has been confirmed that any
important biological activity of GAS5 must be
mediated through the introns.Gas5 can affect activity
of glucocorticoid receptors(GR) by combining its
binding domain, thus to influence cellular sensibility
to apoptosis. Maternally expressed gene 3(MEG3), is
derived from an imprinted locus on human
chromosome 14q32, encoding lncRNA (Balik V, et al.,
2013).With the ability of tumor suppressor,MEG3
could inhibit proliferation of breast cancer by
down-regulating gene transcription and DNA
methylation, MEG3 also involved in activities of
p53,inducing apoptosis together (Wang Pengjun, et al.,
2012). It is expected to providing more effective
therapeutic target for breast cancer with intensively
studies of these tumor suppressor genes in breast
cancer tissue.