Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma.
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ABSTRACT:
SUBMITTER: Rothzerg E
PROVIDER: S-EPMC8394133 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Transcriptome profiling of osteosarcoma (OS) by next generation sequencing technology (NGS) has been broadly performed by previous researches, which uncovers a large number protein-coding driver genes, facilitates our understanding of the molecular mechanisms of OS formation, progression and metastasis. Recently, more and more researchers realize the importance of long non-coding RNAs (lncRNAs) on the development of OS. However, few studies focus on discovering driver lncRNAs.Here we collected somatic copy number alterations (SCNAs) and gene expression profiles of 84 samples from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project. The RNA sequencing data detected 13,903 expressed lncRNAs, 157 of which were previously reported to be associated with cancer based on the annotations from Lnc2Cancer database.By analyzing the SNP array data, several significant SCNAs were detected, such as the amplifications on chromosomes 1q, 4q, 17p, 17q, and 19q, and deletions on 1q, 3q, 9p, 10q, and 15q. With the SCNA and gene expression profiles, we identified 167 driver genes by integrative analysis, including 162 novel driver lncRNAs, 2 lncRNAs reported to be associated with OS, and another 3 associated with other cancers. Furthermore, functional characterization and survival analysis revealed that RP11-241F15.10 may function as a tumor suppressor in OS, and loss of function may contribute to activation of Wnt signaling pathway.This study not only facilitates our understanding of the oncogenic or tumor-suppressor role of lncRNAs in OS, but also provides potential therapies for the patients with OS with metastasis or relapse.
| S-EPMC6380806 | biostudies-literature
Project description:Osteosarcoma is a highly malignant tumor, with very high disability and fatality rates. However, the overall prognosis is not optimistic. Pyroptosis is a newly discovered cell death modality accompanied by inflammation, which is closely related to varieties of cancers. In this study, the RNA-seq data were downloaded from public databases, the differences in the expression of the pyroptosis-related genes (PRGs) were identified, and the six PRGs signature was established through the univariate and LASSO Cox analysis. The patients were grouped according to the PRGs signature, and the prognosis between the two groups was further compared. In addition, a ten pyroptosis-related lncRNAs (PRLs) prognostic signature was also constructed. Through functional analysis of the differentially expressed genes (DEGs), the immune-related pathways were found to be enriched. The Pearson correlation analysis showed a strong correlation between the pyroptosis-related biomarkers. Finally, we identified a promising biomarker, CHMP4C, which is highly expressed in osteosarcoma. Overexpression of CHMP4C promoted the proliferation, migration and invasion of the osteosarcoma cell. Our results thus provide new evidence for exploring prognostic biomarkers and therapeutic targets of osteosarcoma.
| S-EPMC9575257 | biostudies-literature
Project description:Background:Numerous studies have reported the relationship between Long non-coding RNAs (LncRNAs) expression and prognosis of osteosarcoma, but less consensus has been reached. Our meta-analysis was conducted to quantitatively assess the relationship between the expression of LncRNAs, prognosis and clinical pathology in osteosarcoma development. Methods:PubMed,Embase,Web of Science,The Cochrane Library,SionMed,CNKI and WanFang databases were carefully searched to identify eligible studies. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic significance of LncRNAs expression in osteosarcoma. Moreover, meta-regression analysis and subgroup analysis were carried out to explore the potential sources of heterogeneity. Results:A total of 20 studies comprising 1749 patients were included in present meta-analysis. The results showed that the over-expression of LncRNA had a significant correlation with overall survival (OS) (HR?=?2.16, 95% CI:1.68-2.79), and was not related to disease free survival (DFS) (HR?=?0.71, 95% CI:0.05-9.53). Subgroup analysis further indicated that LncRNA transcription level was significantly associated with alkaline phosphatase (HR?=?2.13, 95% CI:1.58-2.88) , tumor size (<?8/???8:HR?=?1.97, 95% CI: 1.55-2.62) , metastasis (yes/no: HR?=?2.14,95% CI:1.15-3.97) , distant metastasis(presence/absence: HR?=?4.02, 95% CI:3.05-5.23) and Enneking stage(IIA /IIB-III:HR?=?3.2, 95% CI:2.48-4.14), but not associated with age (??25/?>?25:HR?=?1.01, 95% CI:0.78-1.3), gender(female/male: HR?=?1.15, 95% CI: 0.96-1.37), tumor site (femur,tibia/elsewhere:HR?=?1.15, 95% CI:0.94-1.4) and chemotherapy (yes/no: HR?=?1.45, 95% CI:0.46-4.63). Conclusions:This study demonstrated that abnormal LncRNAs expression might be potential prognostic markers to predict worse overall survival in osteosarcoma patients. However, the cut-off values may be the source of heterogeneity.
| S-EPMC6303364 | biostudies-other
Project description:Despite recent efforts in discovering novel long non-coding RNAs (lncRNAs) and unveiling their functions in a wide range of biological processes their applications as biotechnological or therapeutic tools are still at their infancy. We have recently shown that AS Uchl1, a natural lncRNA antisense to the Parkinson's disease-associated gene Ubiquitin carboxyl-terminal esterase L1 (Uchl1), is able to increase UchL1 protein synthesis at post-transcriptional level. Its activity requires two RNA elements: an embedded inverted SINEB2 sequence to increase translation and the overlapping region to target its sense mRNA. This functional organization is shared with several mouse lncRNAs antisense to protein coding genes. The potential use of AS Uchl1-derived lncRNAs as enhancers of target mRNA translation remains unexplored. Here we define AS Uchl1 as the representative member of a new functional class of natural and synthetic antisense lncRNAs that activate translation. We named this class of RNAs SINEUPs for their requirement of the inverted SINEB2 sequence to UP-regulate translation in a gene-specific manner. The overlapping region is indicated as the Binding Doman (BD) while the embedded inverted SINEB2 element is the Effector Domain (ED). By swapping BD, synthetic SINEUPs are designed targeting mRNAs of interest. SINEUPs function in an array of cell lines and can be efficiently directed toward N-terminally tagged proteins. Their biological activity is retained in a miniaturized version within the range of small RNAs length. Its modular structure was exploited to successfully design synthetic SINEUPs targeting endogenous Parkinson's disease-associated DJ-1 and proved to be active in different neuronal cell lines. In summary, SINEUPs represent the first scalable tool to increase synthesis of proteins of interest. We propose SINEUPs as reagents for molecular biology experiments, in protein manufacturing as well as in therapy of haploinsufficiencies.
| S-EPMC4429562 | biostudies-literature
Project description:Thousands of long non-coding RNAs (lncRNAs) have been identified in mammalian cells. Some have important functions and their dysregulation can contribute to a variety of disease states. However, most lncRNAs have not been functionally characterized. Complicating their study, lncRNAs have widely varying subcellular distributions: some reside predominantly in the nucleus, the cytoplasm or in both compartments. One method to query function is to suppress expression and examine the resulting phenotype. Methods to suppress expression of mRNAs include antisense oligonucleotides (ASOs) and RNA interference (RNAi). Antisense and RNAi-based gene-knockdown methods vary in efficacy between different cellular compartments. It is not known if this affects their ability to suppress lncRNAs. To address whether localization of the lncRNA influences susceptibility to degradation by either ASOs or RNAi, nuclear lncRNAs (MALAT1 and NEAT1), cytoplasmic lncRNAs (DANCR and OIP5-AS1) and dual-localized lncRNAs (TUG1, CasC7 and HOTAIR) were compared for knockdown efficiency. We found that nuclear lncRNAs were more effectively suppressed using ASOs, cytoplasmic lncRNAs were more effectively suppressed using RNAi and dual-localized lncRNAs were suppressed using both methods. A mixed-modality approach combining ASOs and RNAi reagents improved knockdown efficacy, particularly for those lncRNAs that localize to both nuclear and cytoplasmic compartments.
| S-EPMC4737147 | biostudies-literature
Project description:BACKGROUND: Recent analysis of the mouse transcriptional data has revealed the existence of approximately 34,000 messenger-like non-coding RNAs (ml-ncRNAs). Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. RESULTS: A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir) for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel) strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 x 10(-16)) with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800) in the ml-ncRNAs population. CONCLUSION: Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.
| S-EPMC2410135 | biostudies-literature
Project description:Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Despite the advances in the knowledge of pathogenetic molecular mechanisms and the implementation of more effective drug treatments in recent years, the overall survival rate of patients remains unsatisfactory. The high death rate is mainly due to metastasis of cancer in about half of the cancer patients and the emergence of drug-resistant populations of cancer cells. Improved understanding of cancer molecular biology has highlighted the role of non-coding RNAs (ncRNAs) in colorectal cancer development and evolution. ncRNAs regulate gene expression through various mechanisms, including epigenetic modifications and interactions of long non-coding RNAs (lncRNAs) with both microRNAs (miRNAs) and proteins, and through the action of lncRNAs as miRNA precursors or pseudogenes. LncRNAs can also be detected in the blood and circulating ncRNAs have become a new source of non-invasive cancer biomarkers for the diagnosis and prognosis of colorectal cancer, as well as for predicting the response to drug therapy. In this review, we focus on the role of lncRNAs in colorectal cancer development, progression, and chemoresistance, and as possible therapeutic targets.
| S-EPMC9654895 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are emerging as promising prognostic biomarkers in an expanding list of malignant neoplasms. Here, we sought to investigate the strength of associations between lncRNA signatures and clinical outcomes in osteosarcoma. We conducted a systematic search of the online databases from inception to July 2016. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for the primary endpoints of overall survival (OS), progression-free survival (PFS) or event-free survival (EFS) were extracted and meta-analyzed. Our results manifested that altered lncRNAs expression was markedly associated with worse OS (univariate analysis: HR = 3.20, 95% CI: 2.42-4.24, P = 0.000; multivariate analysis: HR = 2.66, 95% CI: 1.92-3.69, P = 0.000), PFS (HR = 2.05, 95% CI: 1.32-3.18, P = 0.001) and EFS (HR = 4.37, 95% CI: 1.64-11.66, P = 0.003) times among osteosarcoma patients. In the pooled analyses stratified by clinicopathological features, levels of lncRNAs were closely correlated with tumor size (pooled P = 0.001), tumor stage (pooled P = 0.003), and distant metastasis (pooled P = 0.002) in osteosarcoma. The results obtained in our work suggest that altered lncRNA signatures predict unfavorable clinical outcomes and are acceptable to be potential prognostic biomarkers in forecasting prognosis of osteosarcoma.
| S-EPMC5471049 | biostudies-literature
Project description:Antisense (as)lncRNAs are extensively degraded by the nuclear exosome and the cytoplasmic exoribonuclease Xrn1 in the budding yeast Saccharomyces cerevisiae, lacking RNA interference (RNAi). Whether the ribonuclease III Dicer affects aslncRNAs in close RNAi-capable relatives remains unknown. Using genome-wide RNA profiling, here we show that aslncRNAs are primarily targeted by the exosome and Xrn1 in the RNAi-capable budding yeast Naumovozyma castellii, Dicer only affecting Xrn1-sensitive lncRNAs (XUTs) levels in Xrn1-deficient cells. The dcr1 and xrn1 mutants display synergic growth defects, indicating that Dicer becomes critical in the absence of Xrn1. Small RNA sequencing showed that Dicer processes aslncRNAs into small RNAs, with a preference for asXUTs. Consistently, Dicer localizes into the cytoplasm. Finally, we observed an expansion of the exosome-sensitive antisense transcriptome in N. castellii compared to S. cerevisiae, suggesting that the presence of cytoplasmic RNAi has reinforced the nuclear RNA surveillance machinery to temper aslncRNAs expression. Our data provide fundamental insights into aslncRNAs metabolism and open perspectives into the possible evolutionary contribution of RNAi in shaping the aslncRNAs transcriptome.
2019-08-21 | GSE129232 | GEO
Project description:Recent studies have emphasized an important role for long non-coding RNAs (lncRNA) in epigenetic regulation, development, and disease. Despite growing interest in lncRNAs, the mechanisms by which lncRNAs control cellular processes are still elusive. Improved understanding of these mechanisms is critical, because the majority of the mammalian genome is transcribed, in most cases resulting in non-coding RNA products. Recent studies have suggested the involvement of lncRNA in neurobehavioral and neurodevelopmental disorders, highlighting the functional importance of this subclass of brain-enriched RNAs. Impaired expression of lnRNAs has been implicated in several forms of intellectual disability disorders. However, the role of this family of RNAs in cognitive function is largely unknown. Here we provide an overview of recently identified mechanisms of neuronal development involving lncRNAs, and the consequences of lncRNA deregulation for neurodevelopmental disorders.
| S-EPMC3874560 | biostudies-literature