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The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC. [ABSTRACT FROM AUTHOR]

Transcribed ultraconserved regions (T‐UCRs) are noncoding RNAs derived from DNA sequences that are entirely conserved across species. Their expression is altered in many tumor types, and, although a role for T‐UCRs as regulators of gene expression has been proposed, their functions remain largely unknown. Herein, we describe the epigenetic silencing of the uc.160+ T‐UCR in gliomas and mechanistically define a novel RNA–RNA regulatory network in which uc.160+ modulates the biogenesis of several members of the miR‐376 cluster. This includes the positive regulation of primary microRNA (pri‐miRNA) cleavage and an enhanced A‐to‐I editing on its mature sequence. As a consequence, the expression of uc.160+ affects the downstream, miR‐376‐regulated genes, including the transcriptional coregulators RING1 and YY1‐binding protein (RYBP) and forkhead box P2 (FOXP2). Finally, we elucidate the clinical impact of our findings, showing that hypermethylation of the uc.160+ CpG island is an independent prognostic factor associated with better overall survival in lower‐grade gliomas, highlighting the importance of T‐UCRs in cancer pathophysiology.

Abstract The ultraconserved regions (UCRs) are 481 genomic elements, longer than 200 bp, 100% conserved in human, mouse, and rat genomes. Usually, coding regions are more conserved, but more than 80% of UCRs are either intergenic or intronic, and many of them produce long non-coding RNAs (lncRNAs). Recently, the deregulated expression of transcribed UCRs (T-UCRs) has been associated with pathological conditions. But, differently from many lncRNAs with recognized crucial effects on malignant cell processes, the role of T-UCRs in the control of cancer cell networks is understudied. Furthermore, the potential utility of these molecules as molecular markers is not clear. Based on this information, the present review aims to organize information about T-UCRs with either oncogenic or tumor suppressor role associated with cancer cell signaling, and better describe T-UCRs with potential utility as prognosis markers. Out of 481 T-UCRs, 297 present differential expression in cancer samples, 23 molecules are associated with tumorigenesis processes, and 12 have more clear potential utility as prognosis markers. In conclusion, T-UCRs are deregulated in several tumor types, highlighted as important molecules in cancer networks, and with potential utility as prognosis markers, although further investigation for translational medicine is still needed.

R ments in surgical and other novel treatment strategies. Competing endogenous RNAs ceRNAs are considered as significant post-transcriptional regulators that modulate gene expression via miRNA-mediated regulatory networks. Furthermore, it has been demon- strated that ceRNAs have remarkable functions in the pathogenesis of cancers by modulat- ing the expression of oncogenes or tumor-suppressive genes. The aim of this study was to define novel molecular biomarkers for RCC via in silico analysis. Seven miRNAs which have clinical significance for renal cell carcinomas were exported through miRTarBase database. 1001 genes which are targeted by these 7 miRNAs simultaneously were deter- mined by ComiR database. The genes with T-UCR in their exonic regions and which have the potential ceRNA activities were extracted. Gene expression differences between RCC and normal kidney tissues according to the renal cell carcinoma-associated ceRNAs involving T-UCR were identified by GEPIA. The statistical analysis of the relationship between NRXN3 and PTBP2 genes with RCC was determined by Spearman correlation test. NRXN3 and PTBP2 were found to be significantly associated with RCC p=0.0057; R=-0.29 . The current study demonstrates for the first time that PTBP2 gene is associated with renal cell carcinoma. The results of in silico analysis suppose that PTBP2 gene may have potential tumor suppressor role in RCC and NRXN3 gene may have potential onco- genic activity in RCC. Further in vitro and in vivo studies are required in order to clarify tumor suppressor role of PTBP2 and oncogenic activity of NRXN3 in RCC

Transcribed ultraconserved regions (T‐UCRs) are noncoding RNAs derived from DNA sequences that are entirely conserved across species. Their expression is altered in many tumor types, and, although a role for T‐UCRs as regulators of gene expression has been proposed, their functions remain largely unknown. Herein, we describe the epigenetic silencing of the uc.160+ T‐UCR in gliomas and mechanistically define a novel RNA–RNA regulatory network in which uc.160+ modulates the biogenesis of several members of the miR‐376 cluster. This includes the positive regulation of primary microRNA (pri‐miRNA) cleavage and an enhanced A‐to‐I editing on its mature sequence. As a consequence, the expression of uc.160+ affects the downstream, miR‐376‐regulated genes, including the transcriptional coregulators RING1 and YY1‐binding protein (RYBP) and forkhead box P2 (FOXP2). Finally, we elucidate the clinical impact of our findings, showing that hypermethylation of the uc.160+ CpG island is an independent prognostic factor associated with better overall survival in lower‐grade gliomas, highlighting the importance of T‐UCRs in cancer pathophysiology. [ABSTRACT FROM AUTHOR]

Objectives: Glioblastoma multiforme (GBM) is defined as the most frequent and lethal form of the primary brain tumors in the central nervous system (CNS) in adults. Recent studies have focused on the identification of the new targets for the diagnosis and treatment of GBM and resulted in great interest for miRNAs due to their regulatory effects in cancer pathogenesis. Thus, we aimed to characterize novel molecular biomarkers for GBM by computational analysis. Methods: 118 miRNAs that are clinically related with glioblastoma and proven by experimentally were exported through miRTarBase database. 1016 genes projected by these 118 miRNAs were determined via ComiR database. Subsequently, the genes with transcribed ultraconserved regions (T-UCRs) in their exonic regions were designated and the genes which have potential competing endogenous RNA (ceRNA) activities were extracted. Genes with remarkable expression profile differences between glioblastoma and normal brain tissues among ceRNAs that are associated with glioblastoma involving T-UCR were identified. Results: The statistical analysis of the correlation between PBX3 and NRXN3 genes and glioblastoma was carried out by Spearman correlation test. PBX3 and NRXN3 expression was significantly higher and lower in glioblastoma than in normal brain tissues, respectively. On the other hand, the other genes did not have any remarkable differential expression pattern. Conclusion: Based on the findings of the current study, it is determined that NRXN3 acts as a tumor suppressor gene and NRXN3 gene is downregulated in GBM. PBX3 gene functions as an oncogene and is upregulated in GBM. [ABSTRACT FROM AUTHOR]

The transcribed ultraconserved region (T-UCR) belongs to a new type of lncRNAs that are conserved in homologous regions of the rat, mouse and human genomes. A lot of research has reported that differential expression of T-UCRs can influence the development of various cancers, revealing the ability of T-UCRs as new therapeutic targets or potential cancer biomarkers. Most studies on the molecular mechanisms of T-UCRs in cancer have focused on ceRNA regulatory networks and interactions with target proteins, but the present study reveals an innovative dual-targeted regulatory approach in which T-UCRs bind directly to mRNAs and directly to proteins. We screened T-UCRs that may be related to colorectal cancer (CRC) by performing a whole-genome T-UCR gene microarray and further studied the functional mechanism of T-UCR uc.285+ in the development of CRC. Modulation of uc.285+ affected the proliferation of CRC cell lines and influenced the expression of the CDC42 gene. We also found that uc.285+ promoted the proliferation of CRC cells by directly binding to CDC42 mRNA and enhancing its stability while directly binding to CDC42 protein and affecting its stability. In short, our research on the characteristics of cell proliferation found that uc.285+ has a biological function in promoting CRC proliferation. uc.285+ may have considerable potential as a new diagnostic biomarker for CRC., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests. And all authors have read the journal's authorship agreement and that the manuscript has been reviewed by and approved by all named authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Renal cell carcinoma (RCC) is the most common form of kidney cancers and derived from kidney epithelium. The prognosis of RCC is still poor despite recent developments in surgical and other novel treatment strategies. Competing endogenous RNAs (ceRNAs) are considered as significant post-transcriptional regulators that modulate gene expression via miRNA-mediated regulatory networks. Furthermore, it has been demonstrated that ceRNAs have remarkable functions in the pathogenesis of cancers by modulating the expression of oncogenes or tumor-suppressive genes. The aim of this study was to define novel molecular biomarkers for RCC via in silico analysis. Seven miRNAs which have clinical significance for renal cell carcinomas were exported through miRTarBase database. 1001 genes which are targeted by these 7 miRNAs simultaneously were determined by ComiR database. The genes with T-UCR in their exonic regions and which have the potential ceRNA activities were extracted. Gene expression differences between RCC and normal kidney tissues according to the renal cell carcinoma-associated ceRNAs involving T-UCR were identified by GEPIA. The statistical analysis of the relationship between NRXN3 and PTBP2 genes with RCC was determined by Spearman correlation test. NRXN3 and PTBP2 were found to be significantly associated with RCC (p=0.0057; R=-0.29). The current study demonstrates for the first time that PTBP2 gene is associated with renal cell carcinoma. The results of in silico analysis suppose that PTBP2 gene may have potential tumor suppressor role in RCC and NRXN3 gene may have potential onco-genic activity in RCC. Further in vitro and in vivo studies are required in order to clarify tumor suppressor role of PTBP2 and oncogenic activity of NRXN3 in RCC. [ABSTRACT FROM AUTHOR]

• This study is the first to screen the potential lncRNA biomarkers for cured tuberculosis (TB) in human plasma. • Two lncRNAs were identified as potential novel biomarkers for cured TB. • A cured TB model was established with an AUC (area under the curve) of 0.945. • Three target genes of the two lncRNAs were predicted. • The new strategy provided in this study is different from the existing bacterial tests. Tuberculosis (TB) treatment takes a long time, and a gold standard test to define TB cure is lacking. This may lead to early discharge of TB patients, resulting in an increased risk of disease transmission and drug resistance. Plasma lncRNAs might act as potential biomarkers to evaluate TB cure in an efficient and precise manner. A lncRNA microarray assay was used to screen differentially expressed plasma lncRNAs in untreated TB and cured TB subjects. The expression levels of lncRNAs were verified by qPCR. Target genes of lncRNAs were predicted using a coding–non-coding gene co-expression network and mRNA–lncRNA–miRNA interaction network analysis. The expression levels of lncRNAs uc.48+ (p < 0.001) and NR_105053 (p = 0.03) were found to differ significantly between the untreated TB group and the cured TB group. The predicted target genes of uc.48+ were EP300, BAI1 and NR_105053 were TLR9, MYD88, BAI1, respectively. A predictive model for cured TB was established by the combination of uc.48+ and NR_105053 expression, with a sensitivity of 90.00% and specificity of 86.36%, and an area under the curve (AUC) value of 0.945. lncRNAs uc.48+ and NR_105053 may serve as potential biomarkers to distinguish between untreated TB patients and cured TB subjects. This study provides an experimental basis to evaluate the effect of TB treatment and may also provide new clues to the pathological mechanisms of TB. [ABSTRACT FROM AUTHOR]

The author recognized that some references are excluded and positioned in incorrect places due to the reference manager software after the manuscript [E1] is published. Immediately, the author requested from the journal for the corrections of the errors as follows.

Objective: The objective of this study is to define novel biomarkers for Prostate Cancer (PCa) via in silico analysis that takes PCa-specific miRNAs, finds their combinatorial target genes (potential ceRNAs), selects ones containing Transcribed Ultra Conserved Region (T-UCR) among them and potentiates their relevance with PCa. Methods: Thirty-four miRNAs of which clinical relevances with PCa were proved experimentally were exported via miRWalk database.Using the ComiR database, 859 genes targeted by these 34 miRNAs simultaneously were identified. Genes with ComiR score above 0.911 were taken into account. Genes containing T-UCR and showing potential ceRNA activity were extracted. Among PCa-associated ceRNAs including T-UCR, we identified genes with significant expression differences between PCa and normal prostate tissue using the GEPIA database. The statistical evaluation of the association of NFAT5 and PTBP2 genes with PCa was performed by Spearman correlation test in GEPIA database.Results: PCa-associated ceRNAs cross-matching with genes including T-UCR in their exonic regions were NFAT5, CLK3, PTBP2, CPEB4, MIPOL1 and TCF4. We identified genes with significant expression differences between PCa and normal prostate tissues among PCa-associated ceRNAs including T-UCR. According to this analysis, NFAT5 and PTBP2 genes were significantly less expressed in PCa than in normal prostate tissue while the others didn't show any significant differential expression pattern. NFAT5 and PTBP2 genes were found to be significantly associated with PCa (p=0.000012; R=0.72).Conclusion: All in all, this is the study associating NFAT5 and PTBP2 genes with PCa and giving them tumor suppressive potential for PCa. Still, larger and more comprehensive studies are needed on this issue. [ABSTRACT FROM AUTHOR]

Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma. Genome-wide expression profiling revealed correlations between specific T-UCR expression levels and important clinicogenetic parameters such as MYCN amplification status. A functional genomics approach based on the integration of multi-level transcriptome data was adapted to gain insights into T-UCR functions. Assignments of T-UCRs to cellular processes such as TP53 response, differentiation and proliferation were verified using various cellular model systems. For the first time, our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis. [ABSTRACT FROM AUTHOR]

Introduction: Transcribed ultra-conserved regions (T-UCRs) are a new class of long non-coding RNA molecules transcribed from ultra-conserved regions (UCRs) of the human genome. T-UCRs are extremely conserved in the human, rat, and mouse genomes. Deletions of genomic areas containing UCRs resulted in live mice that developed without distinguishable phenotypes, implying that T-UCRs are involved in developmental processes. In addition, there is increasing evidence that dental follicle tissues exhibit various cellular alterations involving deregulation of protein-coding genes and non-coding RNAs. Accordingly, the main objective of the present study was to determine the clinical significance and distinct expression signatures of non-coding RNA molecules transcribed from ultra-conserved regions in dental follicle tissues of impacted mandibular third molars., Materials and Methods: From March 2021 to December 2021, a total of 42 patients who referred to clinic of oral and maxillofacial surgery department with the indications of impacted mandibular third molar extraction from 38th and 48th positions were enrolled for the study. For the analysis of T-UCR expression levels, real-time quantitative reverse transcription PCR method was used., Results: Findings of the present study indicated that T-UCRs are distinctly expressed in dental follicle tissues of impacted mandibular third molars. The expression of uc.38, uc.112, and uc.338 was found to be significantly increased in the dental follicles of impacted mandibular third molars, indicating a clinical significance of these molecules. In addition, no differences in T-UCR expression were found as a function of demographic characteristics., Conclusions: Collectively, transcribed ultra-conserved elements, such as uc.38, uc.112, and uc.338, are considerably deregulated in the dental follicle tissues of impacted mandibular third molars and might be responsible for the molecular changes acquired by dental follicle tissues of impacted mandibular third molars., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

• T-UCRs are a novel family of non-coding RNAs. • T-UCRs are absolutely conserved (100%) across human, mouse, and rat genomes. • T-UCRs are referred to as the "dark matter" of the human genome. • T-UCRs are involved in the malignant transformation of human tumors. The transcribed ultra-conserved regions (T-UCRs) are a novel family of non-coding RNAs which are absolutely conserved (100%) across orthologous regions of the human, mouse, and rat genomes. T-UCRs represent a small portion of the human genome that is likely to be functional but does not code for proteins and is referred to as the "dark matter" of the human genome. Although T-UCRs are ubiquitously expressed, tissue- and disease-specific expression of T-UCRs have also been observed. Accumulating evidence suggests that T-UCRs are differentially expressed and involved in the malignant transformation of human tumors through various genetic and epigenetic regulatory mechanisms. Therefore, T-UCRs are novel candidate predisposing biomarkers for cancer development. T-UCRs have shown to drive malignant transformation of human cancers through regulating non-coding RNAs and/or protein coding genes. However, the functions and fate of most T-UCRs remain mysterious. Here, we review and highlight the current knowledge on these ultra-conserved elements in the formation and progression of human cancers. [ABSTRACT FROM AUTHOR]

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., (© 2019 Wiley Periodicals, Inc.)

Objectives: Transcribed ultraconserved region (T-UCR) uc.261 is reported to participate in intestinal mucosa barrier damage in Crohn's disease (CD). The aim of this study was to determine the association with disease activity and intestinal permeability. Methods: Uc.261 level in colon mucosa and Harvey-Bradshaw Index (HBI) were evaluated in 20 active CD patients. Uc.261 expression and transepithelial electrical resistance (TEER) were determined in Caco2 and T84 cells treated with tumor necrosis factor alpha (TNF-α), respectively. Body weight, disease activity index (DAI), colon length, histological index (HI), intestinal permeability to FITC-dextran, uc.261, and tight junction proteins (TJPs) levels were evaluated in BALB/C mice treated with saline enema, trinitrobenzene sulfonic acid (TNBS)/ethanol enema, and anti-TNF-α monoclonal antibody injection, respectively. Results: Uc.261 expression was overexpressed in CD patients, TNF-α treated cells, and colitis mice. Uc.261 expression was positively correlated with HBI (r = 0.582, p = 0.007) in CD patients, and positively correlated with TNF-α concentration and negatively correlated TEER in Caco2 and T84 cells (all p < 0.05). Furthermore, uc.261 was positively correlated with DAI (r = 0.824, p = 0.008), HI (r = 0.672, p = 0.021), and intestinal permeability (r = 0.636, p = 0.012), while negatively correlated with body weight (r = –0.574, p = 0.035), colon length (r = –0.866, p = 0.017), and TJP expression (all p < 0.05) in colitis mice. Conclusions: Uc.261 expression was closely correlated with disease activity and intestinal permeability in CD. Anti-TNF-α treatment may play its role through suppressing uc.261 expression in colitis mice. [ABSTRACT FROM AUTHOR]

Lung cancer is the most prevalent and deadliest cancer worldwide. A significant part of lung cancer studies is dedicated to the expression alterations of non-coding RNAs. The non-coding RNAs are transcripts that cannot be translated into proteins. While the study of microRNAs and siRNAs in lung cancer received a lot of attention over the last decade, highly efficient therapeutic option or the diagnostic methods based on non-coding RNAs are still lacking. Because of this, it is of utmost importance to direct future research on lung cancer towards analyzing other RNA types for which the currently available data indicates that are essential at modulating lung tumorigenesis. Through our review of studies on this subject, we identify the following non-coding RNAs as tumor suppressors: ts-46, ts-47, ts-101, ts-53, ts-3676, ts-4521 (tRNA fragments), SNORD116-26, HBII-420, SNORD15A, SNORA42 (snoRNAs), piRNA-like-163, piR-35127, the piR-46545 (piRNAs), CHIAP2, LOC100420907, RPL13AP17 (pseudogenes), and uc.454 (T-UCR). We also found non-coding RNAs with tumor-promoting function: tRF-Leu-CAG, tRNA-Leu, tRNA-Val (tRNA fragments), circ-RAD23B, circRNA 100146, circPVT1, circFGFR3, circ_0004015, circPUM1, circFLI1, circABCB10, circHIPK3 (circRNAs), SNORA42, SNORA3, SNORD46, SNORA21, SNORD28, SNORA47, SNORD66, SNORA68, SNORA78 (snoRNAs), piR-65, piR-34871, piR-52200, piR651 (piRNAs), hY4 5' fragments (YRNAs), FAM83A-AS1, WRAP53, NKX2-1-AS1 (NATs), DUXAP8, SFTA1P (pseudogene transcripts), uc.338, uc.339 (T-UCRs), and hTERC. [ABSTRACT FROM AUTHOR]

Transcribed ultraconserved regions (T-UCRs) are genomic regions conserved across large evolutionary distances, which encode for noncoding RNAs that serve as regulators of gene expression. Although T-UCRs have been linked to multiple aspects of mammalian gene regulation, the roles of their extreme evolutionary conservation remain largely unexplained. Growing body of literature is now focusing on T-UCRs as potential cancer biomarkers or as new drug targets. Here we present an overview of the discoveries so far published about the role of T-UCR in cancer and disease., (© 2017 Elsevier Inc. All rights reserved.)

As a common toxic metal, lead has significant neurotoxicity to brain development. Long non-coding RNAs (lncRNAs) function in multiple biological processes. However, whether lncRNAs are involved in lead-induced neurotoxicity remains unclear. Uc.173 is a lncRNA from a transcribed ultra-conservative region (T-UCR) of human, mouse and rat genomes. We established a lead-induced nerve injury mouse model. It showed the levels of Uc.173 decreased significantly in hippocampus tissue and serum of the model. We further tested the expression of Uc.173 in serum of lead-exposed children, which also showed a tendency to decrease. To explore the effects of Uc.173 on lead-induced nerve injury, we overexpressed Uc.173 in an N2a mouse nerve cell line and found Uc.173 had an inhibitory effect on lead-induced apoptosis of N2a. To investigate the molecular mechanisms of Uc.173 in apoptosis associated with lead-induced nerve injury, we predicted the target microRNAs of Uc.173 by using miRanda, TargetScan and RegRNA. After performing quantitative real-time PCR and bioinformatics analysis, we showed Uc.173 might inter-regulate with miR-291a-3p in lead-induced apoptosis and regulate apoptosis-associated genes. Our study suggests Uc.173 significantly inhibits the apoptosis of nerve cells, which may be mediated by inter-regulation with miRNAs in lead-induced nerve injury.

Spinal cord plays an important role in the transmission and modulation of nociceptive information. Global changes in gene expression in the spinal cord contribute to the induction and maintenance of neuropathic pain. Transcribed Ultraconserved Regions (T-UCRs), a novel class of long noncoding RNAs, can regulate gene expression at both transcriptional and post-transcriptional levels and are related to many human diseases such as cancer, Alzheimer's disease, and heart diseases. In this study, we screened abnormal T-UCRs expression in the spinal cord under spinal nerve ligation (SNL)-induced neuropathic pain condition. Microarray data showed the alternation of T-UCRs at the transcriptional level in the spinal cord 10 days after SNL. Among 78 altered T-UCRs, 23 T-UCRs were upregulated by more than 1.5-fold and 55 ones downregulated by less than 0.5-fold after SNL. Hierarchical cluster analysis of T-UCRs expression profiles showed the opposite expression pattern between SNL and sham-operated mice. The quantitative real-time reverse transcription polymerase chain reaction analysis further confirmed the expression patterns of uc.305, uc.189, uc.46, and uc.217 after SNL. The gene ontology annotation and signaling pathway analysis for the T-UCRs host genes indicated that differentially expressed T-UCRs were involved in several intracellular activities and signaling pathways, including Ephrin receptor activity, soluble NSF attachment protein receptor (SNARE) interactions in vesicular transport pathway, and WNT signaling pathway. Collectively, the current data suggest the possible role of T-UCR in the pathogenesis of neuropathic pain. T-UCRs may serve as a new kind of target for the treatment of neuropathic pain.

Pervasive transcription occurs in the human genome to generate thousands of RNA transcripts, and accumulating evidence suggested that the RNA molecules, without protein coding ability, have important roles in diverse biological functions. Long non-coding RNA (lncRNA), with size larger than 200 nt, is a new class of the non-coding RNA that contributes to cancer development and progression. Roles for several lncRNAs in cancers have been characterized and strategies targeting them have inhibitory effects to malignant cells in vitro and in vivo. These findings point to the potential of lncRNAs as prospective novel therapeutic targets in cancers. Recent advance in biological drugs, led by nucleic acid drugs (i.e. siRNAs, antisense oligonucleotides), suggest directions for the development of cancer therapies targeting lncRNAs. Here, we discuss the characteristics of lncRNAs regarding their synthesis, stability and functional role in cells, and emphasize their unique properties that determine their molecular functions. We then discuss the association of lncRNAs with cancers, and illustrate the anticancer effects induced upon modulating the level and function of lncRNAs. We also revisit established methods for targeting RNA molecules and discuss new agents and strategies to attenuate lncRNAs in cancer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)