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miRNA-200 transcriptionally upregulated E-cadherin by ZEB1 repression. This
related closely with the inhibition of EMT and the acquisition of a less aggressive
phenotype. EGF/EGFR signalling actively initiates EMT and this is associated with
reduced expression of miRNA200s. Also, induced restoration of this miRNA is able
to block EGF-mediated induction of EMT and lead to reversal of the EMT pheno-
type (Zhang et al., 2012f).
One should include a comment here that the c-met receptor of HGF is also known
to be targeted by miRNAs. Upregulating the expression of miRNA-199a-3p has been
found to target c-met and reduce the invasive ability of HCC cells (Fornari et  al.,
2010). Tan et  al. (2011) have shown that miRNA-198 directly targets c-met and
binds to a single cognate binding site of c-met 3′UTR and regulates its expression. It
inhibits HGF/c-met signalling of HCC cell migration in Matrigel in vitro assays.
The angiogenic growth factors VEGF and basic fibroblast growth factor (bFGF)
both seem to upregulate the expression of miRNA-16 and miRNA-424. The expres-
sion of primary transcripts primary-miRNA-16-1 and primary-miRNA-16-2, but not
of primary-miRNA-424, was upregulated. Thus both growth factors seem to regu-
late transcription as well as post-transcription maturation process of these miRNAs.
Activated ERα has been reported to inhibit the maturation of primary-miRNA into
pre-miRNA (Yamagata et al., 2009) possibly by impinging upon the function of the
Drosha/Pasha complex. On the other hand, this may not apply as a general rule, for
there are instances where ER do upregulate miRNAs.
It would appear that overexpression of miRNA-16 or miRNA-424 might regulate
VEGF and bFGF function in terms of angiogenic signalling by targeting VEGFR2
and FGFR1 (Chamorro-Jorganes et  al., 2011). The operation of this upregulatory
loop can lead to the amplification of a primary angiogenic signal with the aid of
miRNAs. MiRNA-194 seems to influence angiogenesis by a p53/TSP-1 pathway.
Sundaram et al. (2011) have shown that p53 upregulates miRNA-194 expression and
this then suppresses TSP-1 levels resulting in the promotion of angiogenesis in vitro .
The suppression of TSP-1 is mediated by a single complementary site in the THBS1
gene which encodes TSP-1.
In a preliminary report, Porter et al. (2011) have implicated transforming growth
factor beta (TGF-β) signalling in the regulation of miRNA-21 in glia and neurons.
Hao et  al. (2011) have found that miRNA-483-3p is highly expressed in pancreatic
cancer. They have also provided convincing evidence that forced enhancement of
miRNA-483-3p in pancreatic cancer cell lines is able to downregulate the expression
of Smad4 and also promote cell proliferation. MiRNA-128a has been shown to bind
to the 3′UTR region of the gene encoding the TGF-βRI receptor protein and nega-
tively regulate its expression in MCF breast cancer cells (Masri et al., 2010).
miRNAs in EMT, and Cell Motility and Invasion
The establishment of the possible involvement of miRNA in metastatic spread
has touched many steps of metastatic cascade. The approach to this has included
investigating if the biological faculty of invasion and cell motility, induction of
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