Consistentlydownregulated microRNAs including let-7, miR-133a and miR-200a were associatedwith key oncogenic mRNA. let-7a has been shown to negatively regulates KRAS whichis associated with poor prognosis.
Additionally, miR-133a/btargets pyruvate kinase M2, a key regulator of cancer metabolism.175However, arecent study by Chen et al in whichthey performed meta-analysis of thirteen miRNA profiling studies has indicatedthat the miRNA-99 family (miR-99a, miR-99b and miR-100) are downregulated inHNSCC and that this family of miRNA are associated with aberrant cellproliferation, migration, and enhanced apoptosis (Chenet al., 2012). This is supported by0 data thatshow miRNA–99a/100 promoted apoptosis in oesophageal squamous cell carcinomas (Sunet al.
, 2013a). Additionally, miR-133ais also significantly reduced in head and neck squamous cell carcinoma (HNSCC)and that miR-133a (mimic) treatment resulted in a decrease in cellproliferation, migration and invasion via the repression of the mirR133a targetmoesin in HNSCC cell lines. Silencing of moesin also inhibited cell proliferation, migration and invasionactivities (Kinoshita et al., 2012).
Downregulation of microRNA inhead and neck cancer is also evident in patient samples. Patient samplesfrom both tissue and saliva showed that miR-200a is significantly downregulated in HNSCC patients and that miR-200a functions as a tumoursuppressor repressing ZEB1 and ZEB2 expression and regulatingepithelial-mesenchymal transition and cell migration (Korpal et al., 2008).In addition to the frequent microRNAsthat are downregulated in HNSCC, there are also microRNAs that frequentlyupregulated. The vast majority of cancer,including head and neck cancer, have been shown to have an upregulation of miR-21where miR-21 via targets such as PTEN and the programmed cell death 4 (PDCD4)gene, resulted in consistent increases in cell proliferation, invasion andmetastases 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 elevatedHNSCCs with high miR-196a found in eight head and neck cancer cell lines wasfound to be more proliferative, migratory and invasive compare to the onlyHNSCC in the panel HN5. Additionally, elevated miR-196a was found to induceepithelial to mesenchymal transition as well as increasing radioresistance inhead and neck cancer cell lines.
(Suh et al., 2014b).