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the oncogenic process. MiRNA-520c and miRNA-373 upregulated the expression
of MMP9 and promoted invasive behaviour of human fibrosarcoma HT1080 cells
(Liu and Wilson, 2012). In this study, the effect of the miRNAs was not a result of
directly binding to the MMP promoter, but via binding to mTOR and SIRT1 and
suppressing their translation, resulting in activation of the Ras/Raf/MEK/ERK sig-
nalling pathway and of NF-κB. Of course this would result in enhanced cell migra-
tion and growth as the authors claimed. This is too complex a situation that warrants
further study and confirmation. Nonetheless miRNA-373 and 520c are both able to
downregulate many splice variants of CD44 and stimulate cell migration (Yang et al.,
2009b). Iczkowski (2011) has confirmed that both miRNA-373 and miRNA-520c
reduced the expression of CD44s (standard variant) in prostate cancer cells. Cell
proliferation and invasion were restored upon re-expression of CD44s. But then it is
necessary to recognise while relating CD44 to cell migration and proliferation that
CD44 splice variants display markedly differential expression in different tumour
systems.
Heightened expression of miRNA-373 in HCC samples and in HCC cells pro-
moted cell proliferation. Apparently miRNA-373 targets the gene encoding the pro-
tein phosphatase 6 catalytic subunit, which negatively regulates the cell cycle (Wu
et al., 2011b). The miRNAs-371/373 and miRNA-302 are overexpressed in all
malignant germ cell tumours and serum levels of the same might potentially serve
as disease markers (Murray et al., 2011). However, in colon cancer, miRNA-373 is
downregulated by methylation (Tanaka et al., 2011). It is needless to point out that
it is generally accepted that miRNAs can promote or suppress cancer-related pro-
cesses as discussed earlier, but whilst this relates to different miRNA species equally
it is conceivable that opposite outcomes might result upon the prevailing signal-
ling conditions. Another suppressor gene that might be targeted by miRNA-373 is
Lats2. Lats2 appears to be directly inhibited by miRNA-373 and their expression
is inversely related (Lee et al., 2009). Hence much caution is required in designing
experimental protocols and interpreting the data concerning miRNAs and CD44 vari-
ants in TXNIP function in tumours.
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