MicroRNAs are key regulators in gene SP600125 expression that could play a role in HNSCC tumorigenesis. miRNAs are a class of highly conserved small noncoding RNAs, that are known to alter gene expression post-transcriptionally. miRNAs have been shown to act through base pairing with the 30-untranslated region of the target mRNA, resulting in the ability to impede translation of targeted mRNA. Blocking of the mRNA leads to the cleavage/or translational repression of the targeted mRNA. Exerting control in the repression of targeted mRNA in combination with other regulatory elements, such as transcription factors have been implicated in dysregulation of critical players in major cellular pathways by mediating cell differentiation, Screening Libraries proliferation and survival. The dysregulation and dysfunction caused by these unique endogenously expressed miRNAs have been shown to be involved in human diseases and implicated in various types of cancers. Increasing evidence has shown that miRNAs have the distinctive ability to function as tumor suppressors or oncogenes. Alterations within the gene transcript have been shown to be critical in tumorigenesis and cancer progression. In recent years, comprehensive profiling analysis of miRNAs has been used to identify aberrantly expressed miRNAs. miR-128 is one of the miRNAs, which has been shown to be down-expressed in several types of cancer including prostate cancer, glioma and non-small cell lung cancer, and to inhibit cancer cell growth and invasion when it is constitutively expressed. Evidence suggests that miR- 128 may play a central role in cellular proliferation by regulating BMI-1, E2fa, and other regulatory element such as transcriptional WEE1-a tyrosine kinase, which phosphorylates CDK1. In contrast to these studies, Myatt et al. have demonstrated that miR-128 is highly expressed in endometrial cancer. There are still no data available for the expression and function of miR-128 in HNSCC. In the present study, we analyzed the function of miR-128 and its putative targets using HNSCC cells and tumor xenograft models. Our results showed that enforced expression of miR-128 inhibited the HNSCC cell proliferation and tumor xenograft growth by mediating the expression of BMI-1, BAG-2, BAX, H3f3b, and Paip2 mRNAs, suggesting that miR-128 might act as a tumor suppressor. miRNAs are recognized as a class of gene modulators regulating various physiological and pathological events. The miRNAs are predicted to regulate the expression of over 30% of all genes and may account for some of the aberrant gene expression in cancer cells. miR-128 is uniquely encoded by two distinct genes, miR-128a and miR-128b, which are processed into an identical mature sequence. miR-128a and miR-128b are both intronic, embedded in the R3HDM1 gene on chromosome 2q21.3 and ARPP21 gene on chromosome 3p22, respectively. The molecular and cellular functions of miR-128 are expressed in numerous pathways and organs within the body. TargetScan 5.0 has categorized and predicted targets of miR-128 in both conserved and non-conserved sites. Intriguingly, miR-128 is shown to be down-regulated with age, affecting genetic diseases, and is shown to function as a tumor suppressor. Specifically, miR-128 is shown to block major singling pathways such as ERK and AKT in tumor development, resulting in the inhibition of proliferation, metastasis and angiogenesis in non-small cell lung cancer.