The histone modifiers (HMs) are crucial for chromatin dynamics and gene expression; however, their dysregulated expression has been observed in various abnormalities including cancer. In this study, we have analyzed the expression of HMs in microarray profiles of head and neck cancer (HNC), wherein a highly significant overexpression of p21-activated kinase 2 (PAK2) was identified which was further validated in HNC patients. The elevated expression of PAK2 positively correlated with enhanced cell proliferation, aerobic glycolysis and chemoresistance and was associated with the poor clinical outcome of HNC patients. Further, dissection of molecular mechanism revealed an association of PAK2 with c-Myc and c-Myc-dependent PKM2 overexpression, wherein we showed that PAK2 upregulates c-Myc expression and c-Myc thereby binds to PKM promoter and induces PKM2 expression. We observed that PAK2–c-Myc–PKM2 axis is critical for oncogenic cellular proliferation. Depletion of PAK2 disturbs the axis and leads to downregulation of c-Myc and thereby PKM2 expression, which resulted in reduced aerobic glycolysis, proliferation and chemotherapeutic resistance of HNC cells. Moreover, the c-Myc complementation rescued PAK2 depletion effects and restored aerobic glycolysis, proliferation, migration and invasion in PAK2-depleted cells. The global transcriptome analysis of PAK2-depleted HNC cells revealed the downregulation of various genes involved in active cell proliferation, which indicates that PAK2 overexpression is critical for HNC progression. Together, these results suggest that the axis of PAK2–c-Myc–PKM2 is critical for HNC progression and could be a therapeutic target to reduce the cell proliferation and acquired chemoresistance and might enhance the efficacy of standard chemotherapy which will help in better management of HNC patients.

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Dental caries is a multifactorial disease that affects a large proportion of the population with both genetic and environmental factors contributing to the disease. Even in healthy oral environmental conditions, some individuals are susceptible to dental caries due to potential genetic contribution. Antimicrobial peptides are expressed in oral cavity and play an important role against microbial colonization and form an important first line defense against cariogenic bacteria. In the present study, we attempt to identify genetic variants that would cause significant functional impact towards susceptibility to dental caries. We investigated single nucleotide polymorphisms (SNPs) of beta-defensin 1 (DEFB1) as predictors of dental caries in tamil ethnic population. A total of 120 subjects were recruited for this study, which included 60 dental caries patients (DMFT>5) and 60 healthy controls (DMFT=0). Three SNPs of 5’UTR regulatory elements of DEFB1 were genotyped by PCR followed by Sanger sequencing. The genotypes associated with susceptibility to caries were found to be significant between rs11362 (p=.025, odds ratio = 3.72, 95% confidence interval (CI) = 1.289-10.742), rs1799946 (p=.023, odds ratio=4.32, 95% CI = 1.33-14.028) gene polymorphisms and risk of dental caries (DMFT>5) in tamil ethnicity. The variant genotype GG of rs1800972 polymorphism was found to be high in cases than controls but was not significant (p=0.136). Our data suggested that β-defensin 1 polymorphisms play a role in the susceptibility to dental caries.

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