MicroRNAs are tiny RNA molecules which serve as important posttranscriptional regulators of gene expression. Dysregulated expression of microRNAs has been observed in human cancers, indicating that microRNAs may function as oncogenes or as tumor suppressors. To date, the microRNAs encoded by the oncogenic miR-17-92 cluster, and its paralog the miR-106b-25 cluster, are among those which are differentially expressed in human cancers. In this study, we examined and confirmed the over-expression of these clusters in hepatocellular carcinoma and in hepatoma-derived cells. At least 50% of the tumor samples showed a greater than two-fold increase in the expression for miR-18 and for the miR-106b-25 cluster when compared with the corresponding paired non-tumor samples. Knock-down studies for the miR-106b-25 cluster, which includes miR-106b, miR-93 and miR-25, showed that the expression of the cluster is necessary for cell proliferation and for anchorageindependent growth. In tumors with high expression of this cluster, reduced expression of the BH3-only protein Bim, a miR-25 target, was observed. We further identified the transcription factor E2F1 as a target gene for miR-106b and miR-93 and it is likely that one of the roles of the miR-106b-25 cluster is to prevent excessively high E2F1 expression, which may then cause apoptosis. We conclude that there is aberrant expression of microRNAs encoded by the oncogenic miR-17-92 cluster and the miR-106b-25 cluster in hepatocellular carcinoma. The consistent overexpression of the miR-106b-25 cluster and its role in cell proliferation and anchorage-independent growth points to the oncogenic potential of this cluster. (Cancer Sci 2009; 100: 1234-1242) M icroRNAs (miRNAs) are small, endogenous RNA molecules which are transcribed as long primary transcripts, processed to the precursor miRNAs (pre-miRNA), and further processed to yield approximately 22-nucleotide duplexes of which one arm gives rise to the mature miRNA.(1) Depending on the degree of complementarity, binding of miRNA to its target mRNA can result in either cleavage of the target or in translation repression.(2-4) Despite a comprehensive registry of known miRNAs and the genes which encode them (http://microrna.sanger.ac.uk/sequences/), knowledge of exactly which mRNA and processes each miRNA regulates is incomplete. Studies have shown that miRNAs can influence diverse pathways and affect many physiological processes including metabolism, development, differentiation, and apoptosis.(5-8) Altered expression of miRNAs has been demonstrated in various human cancers including chronic lymphocytic leukemia, (9) lung cancer, (10)(11)(12) colorectal neoplasia, (13,14) breast cancer, (15) and several types of lymphoma. (16)(17)(18)(19) This suggests that miRNAs might function as oncogenes or as tumor suppressors. (20) MicroRNA genes can occur in clusters and these are transcribed as polycistronic transcripts. To date, the miR-17-92 cluster is the best characterized. The miRNAs encoded by this cluster are overexpressed in many ...

Experiments at 8.0 MPa and 277.15 K were carried out in different porous media, such as silica sand and activated carbon, to observe the formation and dissociation of methane hydrate in a specially designed crystallizer for mophology observation. In silica sand bed, we observed a clear hydrate front moving across the bed in the crystallizer at the experimental conditions with 50 and 100% water saturation. The hydrate crystals were observed to form in the interstitial pore space available between the silica sand particles. Whereas in activated carbon bed experiments, hydrates were observed to nucleate on the surface of the activated carbon grain and then dissociate within the stable hydrate formation region. For the first time, we were able to observe this behavior of transient hydrate crystal formation/dissociation in the stable hydrate region in porous media. We postulated that the particle size, pore space, and water saturation level may play a role in the above phenomenon. A clear hydrate front movement across the crystallizer and stable hydrate formation were observed when smaller sized activated carbon grains were used. In all of the experiments, the hydrate crystals were seen to form in the interstitial pore space between the porous media. Our results show that pore space and its interconnectivity play an important role in methane hydrate formation in porous media consisting of silica sand or activated carbon.

Interethnic differences in warfarin dosing in Asian subjects may result from other genetic, dietary, or environmental influences; however, these novel variants in the gene warrant further characterization through functional studies.