Biology Reference
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oestrogen (Leivonen et al., 2009; Pandey and Picard, 2009). On the other hand, the
biogenesis of some miRNAs may be suppressed by ERα.
In this context it would be of interest to note miRNA-26a can regulate ERα and
PR. Using HCC cells, Chen et  al. (2011a) have shown that miRNA-26a can down-
regulate ERα and inhibit growth promotion by oestradiol. In the opposite mode of
function in endometrial adenocarcinoma activated ER are said to upregulate the
expression of tumour-suppressor Let-7 family miRNAs and miRNA-27a leading to
the suppression of Bax and so increase bcl2/Bax ratio and promote cell proliferation
and enhance cell survival. Seven Let-7 family members and miRNA-27a that were
upregulated by ER were able to bind Bax transcripts but not Bcl2 transcripts (Zhang
et al., 2012b). Although these authors have made a persuasive case, one cannot rec-
oncile this with the tumour-suppressor properties of Let-7miRNAs. One could be
losing sight here of the fact that ERα and ERβ exert opposite effects on prolifera-
tion; so it is essential to know which ER is involved in the given experimental con-
ditions. Also Let-7miRNAs suppress stem cell pluripotency and oppose the effects
of miRNA-290 cluster which promote pluripotency. This functional disparity is due
to the ability of miRNA-290 to maintain the expression of Lin28 which inhibits the
maturation of Let-7. The pluripotency transcription factors OCT4, SOX2, REX1, and
NANOG induce miRNAs that promote pluripotency and cell survival, whilst Let-7s
inhibit pluripotency (Li and He, 2012).
Bao et  al. (2011b) found that CD44 binds to HER2 and inhibits the expression
of mi-RNA139, which in turn downregulates the expression of CXCR4 (C-X-C
chemokine receptor type 4). This chain of events has been attributed with loss of
the invasive phenotype. These authors state that HER2 and CD44 are the initiators
of invasive activity of cultured gastric cancer cells and loss of their expression sup-
presses tumour growth. In human gastric cancer, high levels of HER2, CD44, and
CXCR4, and reduced levels of miRNA-139 correlated with metastasis to the lymph
nodes.
Among other systems examined is the IGFR signalling pathway. MiRNA-223
reportedly targets IGF-1R and its downstream signalling pathway and inhibits cell
proliferation (Jia et al., 2011). In a similar vein, miRNA-375 seems to target IGF-1R
to achieve inhibition of growth and metastasis of ESCC (oesophageal squamous
cell carcinoma). MiRNA-375 is downregulated by promoter methylation in pri-
mary ESCC, and furthermore the downregulation has significantly correlated with
advanced stage, the presence of distant metastasis ( p <0.0001) and poor prognosis
(Kong et al., 2012). MiRNA-470, miRNA-669b and miRNA-681 also target and sup-
press IGF-1R (Liang et al., 2011a).
Hepatocyte growth factor (HGF) has been found to downregulate the expression
of miRNA-200c and miRNA-27b. Non-small cell lung carcinoma (NSCLC) have
been reported to show downregulated expression MiRNA-200c and the expression
status was associated with poor differentiation and high lymph node metastases. The
aggressive nature is compatible with the reduced expression of E-cadherin (Ceppi
et  al., 2010). Expression of the transcription factor ZEB1 (zinc-finger E-box 1), a
target of miRNA-200c, was upregulated with further downstream downregulation of
E-cadherin (Susuki et  al., 2011). Earlier, Tryndyak et  al. (2010) demonstrated that
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