Highlighting transcribed ultraconserved regions in human diseases

Abstract

Ultraconserved regions (UCRs) are 481 DNA segments longer than 200 bp in length that are completely conserved among human, mouse, and rat and, extremely conserved across disparate taxa. More than 90% of UCRs are transcribed (T‐UCRs) in normal tissues, but most of them remain uncharacterized. In addition, it was demonstrated that T‐UCRs have a tissue‐specific expression, and a differential expression profile between tumors and other diseases, which suggests that most of T‐UCRs may have an important role in cell processes. However, there is little information about T‐UCR characterization or about their molecular mechanisms of action. Taking this into account, in this study, we aim to summarize deregulated T‐UCRs in human diseases, emphasizing the ones with stronger functional evidences that are associated with important cell pathways and have a detailed molecular characterization. This article is characterized under: RNA in Disease and Development > RNA in Disease Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

Subcellular Localization of uc.8+ as a Prognostic Biomarker in Bladder Cancer Tissue

“…Since Calin et al's 2007 study [23], the differential expression of T-UCRs has been described in several types of cancer, and a plethora of studies has been conducted in order to characterize the role of T-UCRs in carcinogenesis [24]. To date, differential expressions of 286 (59.46%) T-UCRs (out of 481) have been associated with several types of tumor and only of 4% of T-UCRs are known molecular details [10]. Interestingly, few T-UCRs are differentially expressed in specific tumors, and this is the case uc.8+ in BlCa.…”

“…In many cases, the function of these intriguing family of long ncRNAs (lncRNAs) is still to be explained; some lncRNAs are likely involved in splicing [7], others map next to transcriptional regulators or developmental genes, suggesting a role related to them [8], others are probably related to cell proliferation, since they show copy number abnormalities in cancer tissues [9]. In literature, molecular details in terms of RNA size and sequence, or mechanisms of action have been described, only for 19 T-UCRs (3.95%) and the subcellular localization has been studied only for 13 (2.7%), highlighting the urgency of better understanding their molecular features [10]. Similar to proteins, lncRNAs exhibit diverse subcellular levels of accumulation extending from predominant nuclear foci to almost exclusively cytoplasmic localization, where they exert distinct regulatory effects [11,12].…”

Transcribed Ultraconserved Regions Are Associated with Clinicopathological Features in Breast Cancer

“…Most of these regions are transcriptionally active (T-UCRs), and 80% are transcribed from genomic elements located in both intra- and intergenic regions, representing a class of long-non-coding RNAs [ 5 ]. The extreme conservation of T-UCRs in non-coding regions and the significant number of deregulated T-UCRs associated with human diseases may be a sign of their importance in physiologic and pathophysiologic processes [ 6 , 7 ]. Most UCRs are known to be transcribed ultraconserved regions (T-UCRs) in normal and malignant tissues [ 6 ].…”

Differentially Methylated Ultra-Conserved Regions Uc160 and Uc283 in Adenomas and Adenocarcinomas Are Associated with Overall Survival of Colorectal Cancer Patients

“…Transcriptional deregulation of T-UCRs has been attributed mainly to hypermethylation of the promoters, as well as to their interaction with microRNAs (miRNAs) [7,8]. During the last decade, increasingly more publications implicate T-UCRs in human diseases and especially in cancer [9]. Indeed, deregulation of specific T-UCRs has been documented in many malignancies, such as hepatocellular carcinoma [10,11], pancreatic [12], prostate [13,14], neuroblastoma [15], lung [16,17], gastric [18], leukemia [19,20] and CRC [19][20][21][22], while they have been associated with the clinical outcome of cancer patients [15].…”