Abstract. Uterine carcinosarcoma (UCS) is a rare but very aggressive cancer of the female reproductive tract with an extremely poor prognosis. With the goal of understanding the role of microRNA (miRNA) dysregulation in these tumors, we profiled the expression of 667 human miRNAs in a panel of eight UCS patients and five benign control primary tissue samples. These expression profiles revealed two important characteristics of UCS. First, compared with the two most common uterine cancers, endometrial endometrioid adenocarcinoma and endometrial serous adenocarcinoma, UCS samples display a virtually unique pattern of miRNA dysregulation with an overlap of only 5% among the three tumor types. In addition, nearly one-third of the miRNAs significantly dysregulated in UCS tissues compared with benign endometrium (32 of 114) lie in a single small (250-kb) imprinted region of chromosome 14q32. These data suggest that the presence of such a global, region-specific disruption substantially contributes to the unique histology and poor outcome of this type of cancer.
Abstract:The imprinted non-coding RNA H19 was discovered nearly thirty years ago yet, to date, its function has not been ascertained. Recently, H19 has been shown to be the primary transcript of the microRNA miR-675. Both H19 and miR-675 are known to be highly expressed in early fetal development and in an array of solid tumors in humans. We examined H19 sequence and secondary RNA structure in the context of therian evolution to begin to understand the relationship between H19, miR-675, development and oncogenesis. Both H19 sequence and, to a somewhat greater extent, secondary RNA structure is conserved, particularly among eutherians. The pattern of secondary RNA structure conservation in which not only is pre-miR-675 highly conserved but also a number of other, smaller hairpins and a stable fold, coupled with the presence several conserved poly-pyrimidine tracts that are putative binding sites for the RNA-binding protein IMP1, suggests that H19 has two functions compatible with a non-coding RNA. The first is as pri-miR-675 and the second is as a stable docking platform for a regulatory RNP composed of the 3' half of the H19 transcript and up to four molecules of IMP1.
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