Koskensalo et al. [44] analyzed the expression of MMP-7 , and Zhao et al. [45] described the expression of MMP-11. In both reports, the results were equivalent: overexpression of MMPs in a panel of GC cases, when compared with normal gastric mucosa, and a significant shorter survival for patients that overexpressed MMPs. selleck screening library MicroRNAs (miRNAs) are a subset of noncoding RNA molecules (21–23 nucleotides in length) that are believed to regulate gene expression [46]. Altered expression of miRNAs has been associated with several diseases, particularly cancer [47]. Recently, Liu et al. [48] performed a genome-wide serum miRNA expression profile in patients with GC and controls, and they identified a set of
five miRNAs (miR-1, miR-20a, miR-27a, miR-34, and miR-423-5p) whose overexpression was positively correlated with tumor stage. In a different study, Li et al. [49] identified a seven-miRNA signature (miR-10b, miR-21, miR-223, miR-338, let-7a, miR-30a-5p, and miR-126) that associates with an increased risk of recurrence and decreased overall survival, even stratifying patients by stage or histology. These results indicate that Akt inhibitor miRNAs may play an
important role in the carcinogenesis and prognosis of GC. Gene silencing in GC can occur mainly because of point mutations, loss of heterozygosity, and promoter hypermethylation [2,3]. A putative gastric tumor suppressor gene whose expression is frequently downregulated in GC is trefoil factor 1 (TFF1) [50], especially by promoter hypermethylation [51]. Tomita et al. [52] reported recently that the peptide hormone gastrin exerts a suppressive effect in gastric carcinogenesis by suppressing TFF1 promoter hypermethylation. Pancreatic duodenal homeobox-1 (PDX1) is another putative tumor suppressor gene whose expression is frequently downregulated in GC [53]. Ma et al. [54] described the mechanism responsible for PDX1 loss of expression in GC as promoter hypermethylation. Many more articles were published last
year reporting gene promoter hypermethylation as a cause of loss of protein Teicoplanin expression in GC. As examples, loss of expression by promoter methylation was described for BCL2L10 [55], XRCC1 [56], the endogenous retrovirus-related gene psiTPTE-HERV [57], HAI-2 [58], and GRIK2 [59]. Nevertheless, it is crucial to understand that the loss of expression of one gene can occur by different mechanisms acting in that particular gene. As an example, Runx3 is considered a gastric tumor-suppressor gene whose expression is frequently downregulated in GC by promoter hypermethylation [60]. However, Lai et al. [61] described recently that Runx3 expression can be negatively regulated at transcriptional level by the microRNA-130b. In another study, Tsang et al. [62] reported that H. pylori virulence factor CagA is able to bind to Runx3, inducing the ubiquitination and degradation of Runx3 by the proteasome machinery.