ontrary, e ogenous NME4 reduced p JNK and MMP9 e pression. Introduction of NME4 in miR 196 overe pressing cells reversed the ef fect of miR 196 on p JNK and MMP9 e pression. Further more, this molecular pathway was also confirmed in another oral cell line. Taken together, these results suggest that miR 196 e erts its effect through selleckbio the NME4 pJNK TIMP1 MMP1 9 path way. High e pression of miR 196a and miR 196b in cancer tissues correlates with the clinical N stage To understand the clinical significance of miR 196, nor mal and cancerous tissues from 54 patients with oral can cer were obtained for analysis. For each tissue sample, the relative miRNA levels were determined, and the results are shown in Figure 5. Both miR 196a and miR 196b were substantially overe pressed in the cancer tissues.

Com pared to their normal counterparts, 96. 3 and 88. 6% of the cancer tissues e hibited greater than 2 fold higher e pression of miR 196a and miR 196b, respectively. On average, miR 196a and miR 196b levels were elevated by 59. 1 and 10. 4 fold, respect ively, in the cancer tissues. To determine miR 196 downstream regulatory mech anism in vivo, si paired normal and cancerous oral cancer tissues were e amined. As e pected, miR 196a and miR 196b were significantly over e pressed in all cancer tissues. Consistent with these cellular findings, the NME4 target molecule was substantially suppressed, and an elevation of phosphorylated JNK and MMP9 protein e pression was observed. These results confirmed that the dysregulation pathway of miR 196 NME4 pJNK MMP molecular a is occurring in oral cancer patients.

To determine the potential association between cancer status and miR 196 e pression, Pearsons chi squared test was used for statistical analysis. The associations of miR 196 e pression with cancer stage and pathological status are shown in Table 1. There was no significant correlation of miR 196 e pression with the pathological T stage, overall stage, differentiation status, alcohol con sumption, cigarette smoking, or betel quid chewing. However, a significant correlation was found between high miR 196 levels and the pathological N stage. These results indicate the clinical signifi cance of the miR 196 molecules in oral cancer. Discussion The dysregulation of miRNAs is associated with malig nant transformation. Previously, miR 196 e pression was shown to be altered in several cancers.

Although some investigators have reported decreased miR 196 e pres sion in cancers, others have observed increased miR 196 e pression. For e ample, miR 196a and miR 196b are down regulated in melanoma and acute lymphoblastic leukemia. However, miR 196a and miR 196b over e pression has been observed in several malignant diseases, including cancers of the esophagus, pancreas, colorectum, AV-951 glioblastoma, and several types of leukemia. High http://www.selleckchem.com/products/BAY-73-4506.html miR 196a levels have also been associated with a poor prognosis in pancreatic cancer, glioblastoma, and oral squamous cell carcinoma. Furthermore, the