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Journal ArticleDOI

Over-expression of CircRNA_100876 in non-small cell lung cancer and its prognostic value.

01 May 2017-Pathology Research and Practice (Pathol Res Pract)-Vol. 213, Iss: 5, pp 453-456
TL;DR: The findings indicate that circRNA_100876 is closely related to the carcinogenesis of NSCLC and it might be served as a potential prognostic biomarker and therapeutic target for NS CLC.
Abstract: Circular RNAs (circRNAs) are a novel type of endogenous RNAs featuring stable structure and high tissue-specific expression. Recently, accumulating evidence has revealed that aberrant circRNAs expression plays important roles in carcinogenesis and tumor progression. However, the expression pattern and biological function of circRNAs in non small cell lung cancer (NSCLC) remain largely unknown. Therefore, the purpose of this study was to clarify the possible role of one of typical circRNAs, circRNA_100876 in NSCLC and to define its prognostic value in NSCLC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of circRNA_100876 in tumor tissues and their adjacent nontumorous tissues in 101 patients with NSCLC. We found that the expression level of circRNA_100876 was significantly elevated in NSCLC tissues when compared with their adjacent nontumorous tissues (P=0.000). Moreover, there was a close correlation between the circRNA_100876 up-regulation expression and lymph node metastasis (P=0.001) and tumor staging (P=0.001) in NSCLC. In addition, Kaplan-Meier survival analysis demonstrated that the overall survival time of NSCLC patients with high circRNA_100876 expression was significantly shorter than those patients with low circRNA_100876 expression (P=0.000). In conclusion, our findings indicate that circRNA_100876 is closely related to the carcinogenesis of NSCLC and it might be served as a potential prognostic biomarker and therapeutic target for NSCLC.
Citations
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Journal ArticleDOI
TL;DR: A review of recent research shows that circular RNAs may function as potential molecular markers for disease diagnosis and treatment and play an important role in the initiation and progression of human diseases, especially in tumours.
Abstract: Circular RNAs, a novel class of endogenous noncoding RNAs, are characterized by their covalently closed loop structures without a 5′ cap or a 3′ Poly A tail. Although the mechanisms of circular RNAs’ generation and function are not fully clear, recent research has shown that circular RNAs may function as potential molecular markers for disease diagnosis and treatment and play an important role in the initiation and progression of human diseases, especially in tumours. This review summarizes some information about categories, biogenesis, functions at the molecular level, properties of circular RNAs and the possibility of circular RNAs as biomarkers in cancers.

1,072 citations


Cites background from "Over-expression of CircRNA_100876 i..."

  • ...To help predict the occurrence and development of NSCLC, doctors use biomarkers in the clinic....

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  • ...Abbreviations AFP: Alpha fetal protein; AFP-L3: Lens culinaris-agglutinin-reactive fraction of AFP; APL: Acute promyelocytic leukemia; CEA: Carcinoembryonic antigen; circRNAs: Circular RNAs; CIRI: CircRNA Identifier; ciRNAs: Circular intronic RNAs; CRC: Colorectal cancer; ecircRNA: Exonic circRNA; EIciRNA: Exon-intron circRNAs; ESCC: Esophageal squamous cell; GC: Gastric cancer; HCC: Hepatocellular carcinoma; Hif: Hypoxia-inducible factor; IRES: Internal ribosome entry site; LSCC: Laryngeal squamous cell cancer; NSCLC: Nonsmall-cell lung cancer; RCA: Rolling circle amplification; RNA-seq: RNA sequencing; snRNP: Small nuclear ribonucleo proteins Acknowledgements This work was supported by National Key Technology Research and Development program of the Ministry of Science and Technology of China(2014BAI04B02) (to M W)....

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  • ...Lung cancer, which causes cancer-related deaths worldwide, comprises non-small-cell lung cancer (NSCLC) and small-cell lung cancer....

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  • ...Cheng Wang et al. have demonstrated that miR-483-5p, miR-193a-3p, miR-25, miR-214 and miR-7 can potentially be used as biomarkers for diagnosing NSCLC patients [55]....

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  • ...Coincidentally, up-regulated circRNA 100876 in NSCLC was found to closely correlate with lymph node metastasis (P = 0.001) and tumour staging (P = 0.001)....

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Journal ArticleDOI
TL;DR: The current understanding of biogenesis and gene regulatory mechanisms of circRNAs is provided, the recent studies oncircRNAs as potential diagnostic and prognostic biomarkers are summarized, and the major advantages and limitations of circ RNAs as novel biomarkers based on existing knowledge are highlighted.

515 citations

Journal ArticleDOI
TL;DR: Twenty state-of-the-art computational models of predicting miRNA-disease associations from different perspectives are reviewed, including five feasible and important research schemas, and future directions for further development of computational models are summarized.
Abstract: Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules with a variety of biological functions. Studies have shown that circRNAs are involved in a variety of biological processes and play an important role in the development of various complex diseases, so the identification of circRNA-disease associations would contribute to the diagnosis and treatment of diseases. In this review, we summarize the discovery, classifications and functions of circRNAs and introduce four important diseases associated with circRNAs. Then, we list some significant and publicly accessible databases containing comprehensive annotation resources of circRNAs and experimentally validated circRNA-disease associations. Next, we introduce some state-of-the-art computational models for predicting novel circRNA-disease associations and divide them into two categories, namely network algorithm-based and machine learning-based models. Subsequently, several evaluation methods of prediction performance of these computational models are summarized. Finally, we analyze the advantages and disadvantages of different types of computational models and provide some suggestions to promote the development of circRNA-disease association identification from the perspective of the construction of new computational models and the accumulation of circRNA-related data.

473 citations

Journal ArticleDOI
TL;DR: The characteristics, functions, and mechanisms of action of circRNAs in cancer are highlighted and an overview of recent progress in the circRNA field is provided and future application of circ RNAs as cancer biomarkers and novel therapeutic targets is provided.
Abstract: Circular RNAs (circRNAs) are a class of single-stranded closed RNA molecules that are formed by precursor mRNA back-splicing or skipping events of thousands of genes in eukaryotes as covalently closed continuous loops. High-throughput sequencing and bioinformatics approaches have uncovered the broad expression of circRNAs across species. Their high stability, abundance, and evolutionary conservation among species points to their distinct properties and diverse cellular functions as efficient microRNAs and protein sponges; they also play important roles in modulating transcription and splicing. Additionally, most circRNAs are aberrantly expressed in pathological conditions and in a tissue-specific manner such as development and progression of cancer. Herein, we highlight the characteristics, functions, and mechanisms of action of circRNAs in cancer; we also provide an overview of recent progress in the circRNA field and future application of circRNAs as cancer biomarkers and novel therapeutic targets.

290 citations

Journal ArticleDOI
TL;DR: The current state of knowledge regarding circRNAs, their synthesis, function, and association with cancer are considered, and some of the challenges that remain to be resolved are reviewed if this emerging class of RNAs are really to become useful in the clinic.

264 citations

References
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Journal ArticleDOI
21 Mar 2013-Nature
TL;DR: It is found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7.
Abstract: Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.

5,922 citations

Journal ArticleDOI
21 Mar 2013-Nature
TL;DR: This study serves as the first functional analysis of a naturally expressed circular RNA, ciRS-7, which contains more than 70 selectively conserved miRNA target sites, and is highly and widely associated with Argonaute proteins in a miR-7-dependent manner.
Abstract: MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.

5,885 citations

Journal ArticleDOI
01 Feb 2013-RNA
TL;DR: High-throughput sequencing of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease showed that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.
Abstract: Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.

3,310 citations

Journal ArticleDOI
TL;DR: Similar to miRNAs and long noncoding RNAs (lncRNAs), circRNAs are becoming a new research hotspot in the field of RNA and could be widely involved in the processes of life.

1,317 citations

Journal ArticleDOI
TL;DR: The current knowledge about the ciRS-7/miR-7 axis in cancer-related pathways is reviewed and possible models explaining the relevance of coexpressing miR- 7 along with a circRNA inhibitor are discussed.
Abstract: MicroRNAs (miRNA) play important roles in fine-tuning gene expression and are often deregulated in cancer. The identification of competing endogenous RNA and circular RNA (circRNA) as important regulators of miRNA activity underscores the increasing complexity of ncRNA-mediated regulatory networks. Particularly, the recently identified circular RNA, ciRS-7, which acts as a designated miR-7 inhibitor/sponge, has conceptually changed the mechanistic understanding of miRNA networks. As miR-7 modulates the expression of several oncogenes, disclosing the regulation of miR-7 activity will likely advance the understanding of various cancer etiologies. Here, we review the current knowledge about the ciRS-7/miR-7 axis in cancer-related pathways and discuss possible models explaining the relevance of coexpressing miR-7 along with a circRNA inhibitor.

818 citations

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