Hydrophobic interactions should be emphasized because the ATP binding pocket is consisted of a narrow and hydrophobic region.

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In this regard, it has been well documented that one of the key enzymes of the オーダー AP24534 RNAi pathway, Dicer1, has an abnormal expression in dif ferent types of cancer, including OSCCs. Dicer1 is a highly conserved multidomain RNase type III enzyme that plays an essential role in the RNAi and miRNA pathways. The human dicer1 gene, which is located on chromosome 14, spans a region of about 71 kbp and comprises 29 exons. The gene encodes a 218 kDa protein that is found in almost all eukaryotes. Dicer1 is responsible for processing dsRNAs into small interfering RNAs and precursor miR NAs into mature miRNAs. The small non coding RNAs generated by Dicer1 are typically between 20 27 nucleotides long and they function as a guide for the RNA induced silencing complex that targets mRNA for silencing.

The targeting of the mRNA occurs through a base pairing dependent mechanism that leads to translational repression or mRNA degradation. To date, a number of Dicer1 mRNA variants have been described. however, all the reported transcripts have been found to encode the same full length protein because the diversity was observed to affect only the length and composition purchase AT7519 of either their 3 or 5 untranslated regions. Recently, the first mRNA splice variant of the human dicer1 gene bearing a modified coding sequence was identified in neuroblastoma cells. In fact, the dicer1 gene has been predicted to produce several mRNA splice variants in addition to the one found in neuro blastoma cells that encode truncated Dicer1 proteins of varying lengths.

One of these Dicer1 mRNA splice variants termed, Dicer1e, was predicted to pan Akt 阻害剤 translate a 93 kDa protein which was found to be differentially expressed between epithelial and mesenchymal breast cancer cells. Because the expression and function of the Dicer1e protein variant has not been well characterized and it currently remains unclear as to its biological and patho logical significance, this study sought to examine the biological role of the Dicer1e protein variant and determine its relationship, if any, to oral cancer pathogenesis. Results Dicer 1e is overexpressed in OSCC cell lines of epithelial phenotype and in OSCC tissues The human dicer1 gene is predicted to produce several mRNA variants bearing modified coding sequences, one of which, the 93 kDa Dicer1e protein va riant, was reported to be differentially expressed in epithelial and mesenchymal breast cancer cells.

In order to determine the endogenous expression levels of Dicer1e in oral cancer cells, the expression of the 93 kDa Dicer1e protein was examined in a panel of cell lines de rived from tongue squamous cell carcinomas and compared to normal human oral keratinocytes by Western blot analysis. Quantitation of the Dicer1e expression levels demonstrated that the OSCC cell lines of epithelial phenotype, exhibited approximately between 2 and 9 fold dif ferences in Dicer1e protein levels compared to HOKs, whereas, OSCC cell lines of mesenchymal phenotype, exhibited either equivalent or slightly reduced levels of Dicer1e expression. Together, these results corroborated the observed diffe rential expression of Dicer1e in epithelial and mesenchy mal breast cancer cell lines.