Consistently KRAS which is associated with poor

downregulated microRNAs including let-7, miR-133a and miR-200a were associated
with key oncogenic mRNA. let-7a has been shown to negatively regulates KRAS which
is associated with poor prognosis. Additionally, miR-133a/b
targets pyruvate kinase M2, a key regulator of cancer metabolism.175

However, a
recent study by Chen et al in which
they performed meta-analysis of thirteen miRNA profiling studies has indicated
that the miRNA-99 family (miR-99a, miR-99b and miR-100) are downregulated in
HNSCC and that this family of miRNA are associated with aberrant cell
proliferation, migration, and enhanced apoptosis (Chen
et al., 2012). This is supported by0 data that
show miRNA–99a/100 promoted apoptosis in oesophageal squamous cell carcinomas (Sun
et al., 2013a). Additionally, miR-133a
is also significantly reduced in head and neck squamous cell carcinoma (HNSCC)
and that miR-133a (mimic) treatment resulted in a decrease in cell
proliferation, migration and invasion via the repression of the mirR133a target
moesin in HNSCC cell lines. Silencing of moesin also inhibited  cell proliferation, migration and invasion
activities (Kinoshita et al., 2012). Downregulation of microRNA in
head and neck cancer is also evident in patient samples. Patient samples
from both tissue and saliva showed that miR-200a is significantly downregulated
 in HNSCC patients  and that miR-200a functions as a tumour
suppressor repressing ZEB1 and ZEB2 expression and regulating
epithelial-mesenchymal transition and cell migration (Korpal et al., 2008).

In addition to the frequent microRNAs
that are downregulated in HNSCC, there are also microRNAs that frequently
upregulated. The vast majority of cancer,
including head and neck cancer, have been shown to have an upregulation of miR-21
where miR-21 via targets such as PTEN and the programmed cell death 4 (PDCD4)
gene, resulted in consistent increases in cell proliferation, invasion and
metastases as well as poor prognosis (Avissar et al., 2009; Hui et al., 2010; Lu et al.,
2008). Moreover, miR-196a expression has been shown to be elevated
HNSCCs with high miR-196a found in eight head and neck cancer cell lines was
found to be more proliferative, migratory and invasive compare to the only
HNSCC in the panel HN5. Additionally, elevated miR-196a was found to induce
epithelial to mesenchymal transition as well as increasing radioresistance in
head and neck cancer cell lines. (Suh et al., 2014b).  


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