Immortalization and tumorigenic transformation of many human cell types, including human uroepithelial cells (HUCs), are frequently associated with loss of genetic material from the short arm of chromosome 3 (3p). In addition, losses of 3p have been observed in many human cancers including renal cell carcinoma, lung cancer, breast cancer, and bladder cancer. Genetic studies suggest that there are at least two regions on 3p in which tumor suppressor genes might be located, but the precise location of these genes is not known. We studied chromosome 3 losses that were specifically associated with immortalization of five independent human papilloma virus 16 (HPV16) E6‐ or E7‐transformed HUCs. Cytogenetic analysis showed that the smallest common region of deletion was 3p14.1→14.2. Fluorescence in situ hybridization using a 3p13→14‐specific yeast artificial chromosome (YAC) contig showed the precise localization of the breakpoints to be in 3p13 and 3p14.2, thus defining the smallest common overlap of 3p deletions in HPV16 E6‐ or E7‐immortalized HUCs. These results suggest the presence in this region of genes involved in the control of senescence in vitro and possibly tumorigenesis in vivo. Genes Chromosomes Cancer 21:39–48, 1998. © 1998 Wiley‐Liss, Inc.
In mammals, many classes of noncoding RNAs (ncRNAs) are expressed at a much higher level in the brain than in other organs. Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops. The circRNAs are also highly enriched in the brain and increase continuously from the embryonic to the adult stage.Although the functional significance and mechanism of action of circRNAs are still being actively explored, they are thought to regulate the transcription of their host genes and sequestration of miRNAs and RNA binding proteins. Some circRNAs are also shown to have translation potential to form peptides. The expression and abundance of circRNAs seem to be spatiotemporally maintained in a normal brain.Altered expression of circRNAs is also thought to mediate several disorders, including brain-tumor growth, and acute and chronic neurodegenerative disorders by affecting mechanisms such as angiogenesis, neuronal plasticity, autophagy, apoptosis, and inflammation. These extraordinary peculiarities make circRNAs potentially suitable as promising molecular biomarkers, especially of neurodegenerative diseases. This review represents generalisation of the new data about circRNAs, underlining their role in a pathogenesis of the basic neurodegenerative disorders: emphasizing their role in pathogenesis of major neurodegenerative disorders, Alzheimers disease, frontotemporal dementia, and Parkinsons diseases, schizophrenia diseases, ALS with a look toward their potential usefulness in biomarker searching.
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