BackgroundMicroRNAs are a family of 19- to 25-nucleotides noncoding small RNAs that primarily function as gene regulators. Aberrant microRNA expression has been described for several human malignancies, and this new class of small regulatory RNAs has both oncogenic and tumor suppressor functions. Despite this knowledge, there is little information regarding microRNAs in plasma especially because microRNAs in plasma, if exist, were thought to be digested by RNase. Recent studies, however, have revealed that microRNAs exist and escape digestion in plasma.Methodology/Principal FindingsWe performed microRNA microaray to obtain insight into microRNA deregulation in the plasma of a leukemia patient. We have revealed that microRNA-638 (miR-638) is stably present in human plasmas, and microRNA-92a (miR-92a) dramatically decreased in the plasmas of acute leukemia patients. Especially, the ratio of miR-92a/miR-638 in plasma was very useful for distinguishing leukemia patients from healthy body.Conclusions/SignificanceThe ratio of miR-92a/miR-638 in plasma has strong potential for clinical application as a novel biomarker for detection of leukemia.
MicroRNAs (miRNAs) belong to a class of the endogenously expressed non-coding small RNAs which primarily function as gene regulators. Growing evidence suggests that miRNAs have a significant role in tumor development and may constitute robust biomarkers for cancer diagnosis and prognosis. The miR-17-92 cluster especially is markedly overexpressed in several cancers, and is associated with the cancer development and progression. In this study, we have demonstrated that miR-92a is highly expressed in hepatocellular carcinoma (HCC). In addition, the proliferation of HCC-derived cell lines was enhanced by miR-92a and inhibited by the anti-miR-92a antagomir. On the other hand, we have found that the relative amount of miR-92a in the plasmas from HCC patients is decreased compared with that from the healthy donors. Interestingly, the amount of miR-92a was elevated after surgical treatment. Thus, although the physiological significance of the decrease of miR-92a in plasma is still unknown, deregulation of miR-92 expression in cells and plasma should be implicated in the development of HCC.
Chromosomes are highly restricted to specific chromosome territories within the interphase nucleus. The arrangement of chromosome territories is non-random, exhibiting a defined radial distribution as well as a preferential association with specific nuclear compartments, which indicates a functional role for chromosome-territory organization in the regulation of gene expression. In this report, we focus on changes in adipocyte differentiation that are related to a specific chromosomal translocation associated with liposarcoma tumorigenesis, t(12;16). We have examined the relative and radial positioning of the chromosome territories of human chromosomes 12 and 16 during adipocyte differentiation, and detected a close association between the territories of chromosomes 12 and 16 in differentiated adipocytes, an association not observed in preadipocytes. Although further studies are required to elucidate the underlying reasons for the adipocyte-specific translocation of chromosomes 12 and 16, our observations indicate that alteration of relative chromosome positioning might play a key role in the tumorigenesis of human liposarcomas. In addition, these results demonstrate the potential impact of higher order chromatin organization on the epigenetic mechanisms that control gene expression and gene silencing during cell differentiation.
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