Circular RNAs in human cancer
Yumin WangYongzhen MoZhaojian GongXiang YangMo YangShanshan ZhangFang XiongBo XiangMing ZhouQianjin LiaoWenling ZhangXiayu LiXiaoling LiYong LiGuiyuan LiZhaoyang ZengWei Xiong
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Abstract:
CircRNAs are a novel type of RNAs. With the newly developed technology of next-generation sequencing (NGS), especially RNA-seq technology, over 30,000 circRNAs have already been found. Owing to their unique structure, they are more stable than linear RNAs. CircRNAs play important roles in the carcinogenesis of cancer. The expression of circRNAs is correlated with patients' clinical characteristics, and circRNAs play a vital role in many aspects of malignant phenotypes, including cell cycle, apoptosis, vascularization, and invasion; metastasis as a RNA sponge, binding to RBP; or translation. Therefore, it is meaningful to further study the mechanism of interactions between circRNAs and tumors. The role of circRNAs as molecular markers or potential targets will provide promising application perspectives, such as early tumor diagnosis, therapeutic evaluation, prognosis prediction, and even gene therapy for tumors.Keywords:
Circular RNA
To investigate the cell cycle dependent genes involved in gastric tumorigenesis, possibly determining the relationship between the cell cycle and tumorigenesis.MKN45 cells were collected every hour from Oh to 12h after release from G2/M and G1/S blocks. Nine samples (a-i), chosen at key times of the cell cycle, were prepared for RNA isolation and cDNA microarray analysis.In 2001 viable clones, 959 genes showed periodic variations during the cell cycle. Among 2001 genes that were clustered, a series of up-regulated genes were assigned to different cell cycle phases. Many periodically dependent genes in the cell cycle were ubiquitously expressed and participated in various cell physiological functions, such as transcription, translation, ubiquitination and signal transduction. These cell cycle dependent genes could affect cancer cell proliferation, apoptosis, activation of oncogenes and inactivation of tumor suppressor genes.We provided a comprehensive understanding of the gene expression profile involved in gastric cancer cell cycles and laid a foundation for further research on mechanisms of gastric tumorigenesis.
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The development of cancer is a multistep process. To understand oncogenesis and adapt appropriate treatments it is important to have a better definition of a number of factors, including the number and order of oncogenic steps, the identity of the targeted cells and deregulated cellular components, and the genes and pathways altered at each step. We propose here a hypothesis of oncogenesis based on the targeting of the cell cycle in two major steps. Oncogenic hits may occur in two sequences: in one scenario a first oncogenic hit alters the regulation of the G1 phase of the cell cycle leading to a proliferative, premalignant syndrome; oncogenesis is completed when a second oncogenic hit relieves the checkpoints of the late phases of the cell cycle. Alternatively, a genetic alteration may hit the late phases first; this leads to a premalignant disease with signs of senescence. In this scenario, the second hit targets the G1 phase. In the two sequences, oncogenesis is based on the cooperation of two hits targeting different phases of the cell cycle and relieving major checkpoints. Stem cells and progenitor cells of various tissues may be variably sensitive to these hits.
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MicroRNA (miRNA) is an important type of non-coding RNAs with both physiological and pathological functions in human beings. Aberrant expression of miRNAs has been found in tumor tissues and the expression profile of certain groups of miRNAs is now emerging as bio-marker for cancer. It has been confirmed that miRNAs can exert oncogenic or tumor-suppressive functions through repressing the expression of their target genes which play different roles in tumorigenesis. The identification of oncogenic or tumor-suppressive miRNAs allows potential applications of these miRNAs as targets for cancer chemotherapy. In this review, we summarized the well-known cancer-related miRNAs reported in recent years and the roles they played in tumorigenesis and progression by targeting specific genes. Strategies developed to modulate the function or expression of the dysregulated miRNAs are also reviewed with recent examples illustrating their potential applications in cancer chemotherapy. Keywords: MicroRNA, oncogenic, tumor-suppressive, up-regulation, down-regulation, tumorigenesis, cancer chemotherapy.
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MicroRNA (miRNA ) 是在长度的 2123 核苷酸的小非编码的 RNA 分子的簇,它在 post-transcriptional 水平控制目标基因的表达式。最近的研究显示了 miRNA 在 carcinogenesis 起一个必要作用,例如影响房间生长,区别, apoptosis,和房间周期。现在,涉及 carcinogenesis 的 miRNA 的多重答应角色正在出现,并且 miRNA 仔细联系到 epithelialmesenchymal 转变(EMT ) 的进程,这被显示出,癌症干细胞(CSC ) 的规定,肿瘤侵略和移植的开发。miRNA 也充当稳定地在浆液表示的 biomarker 并且为各种各样的癌症的分子的目标治疗提供新目标。这评论的目的是在 carcinogenesis 说明 miRNA 的新角色并且在癌症加亮 miRNA 的新前景临床的申请,例如在血清学的诊断和分子目标的治疗学。
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Circular RNA(circRNA)is a class of endogenous non-coding RNA molecules, which is ubiquitous in eukaryotic cells.They have a closed ring structure, and are mainly composed of exons and / or introns.Circular RNAs have been widely studied in recent years, and studies show that they are remarkably stable, highly conserved and cell- or tissue-specifically expressed.Recently, it has been found that circRNAs can regulate gene expression at the transcriptional or post-transcriptional level by interacting with microRNAs and other molecules.Recent studies have shown that circular RNA may be associated with various diseases, including atherosclerotic vascular disease, prion diseases, neurological disorders, osteoarthritis and diabetes mellitus.In addition, circular RNAs exhibit abnormal expression in a variety of types of cancers, including colorectal cancer, hepatocellular carcinoma, and gastric cancer.Therefore, we believe that circular RNA can be used as a diagnostic marker or therapeutic target of clinical diseases.This article reviews the potential of circular RNA as a diagnostic marker and therapeutic target.
Key words:
Circular RNA; Diagnosis; Prognosis; Biomarkers
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Abstract Background: Breast cancer is a major cause of cancer related death in women worldwide. Molecular diagnostic markers that are detectable in early-stage breast cancer can aid in effective clinical intervention. Circular RNAs are a recently identified group of non-coding RNA with potential role in cancer development and progression. In this study, we aimed to identify circular RNAs specific for early stage breast cancer. Method: Circular RNA expression profile was analyzed in early-stage breast cancer tissues (N=5), matched normal counterparts (N=5) and absolute normal samples (N=5) by RNA-sequencing that enables a comprehensive analysis of RNA expression across the transcriptome. Two different algorithms, find_circ and DCC were used to identify the differentially expressed circular RNAs. Results: A total of 58 and 87 circular RNAs were found to be differentially expressed by find_circ and DCC algorithms, respectively, among which 26 circular RNAs were common. Hsa_circ_0001946 (CDR1-as) was found to be upregulated in early stage breast cancer along with other novel circular RNAs (hsa_circ_0008225, hsa_circ_0007766, hsa_circ_0016601). We also found that a few of the identified circular RNAs harbor microRNA binding sites which can lead to microRNA sponging activity and pre-microRNA sequences which can generate mature microRNAs. The identified circular RNAs that are differentially regulated in early stage breast cancer can be of potential diagnostic/prognostic importance. Conclusion: Circular RNA are differentially expressed in the early-stage breast cancer with potential application in early diagnosis and prognosis. The differentially expressed circular RNA can sequester microRNA and can act as microRNA precursor as well.
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Small nucleolar RNA
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Abstract A new class of regulatory molecules known as microRNAs (miRNAs) is redefining our understanding of the molecular pathways associated with tumorigenesis. These miRNAs are small noncoding RNA (ncRNA) sequences with potent regulatory potential. The aberrant expression of miRNAs has been associated with the development of various tumors. It has been suggested that miRNAs can both regulate and act as tumor‐suppressor genes and oncogenes. Our understanding of the role of miRNAs in head and neck tumorigenesis is in its infancy. However, several recent studies have revealed extensive dysregulation of miRNA in head and neck tumors and have highlighted the potential of certain miRNAs to act as diagnostic and prognostic markers and targets for new therapeutic agents. The intent of this review is to discuss and summarize current findings that point to a significant role for miRNAs in head and neck tumorigenesis. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
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Circular RNA, a class of non-coding RNA, is a new group of RNAs and is related to tumorigenesis. Circular RNAs are suggested to be ideal candidate biomarkers with potential diagnostic and therapeutic implications. However, little is known about their expression in human colorectal cancer. In our study, differentially expressed circular RNAs were detected using circular RNA array in paired tumor and adjacent non-tumorous tissues from six colorectal cancer patients. Expression levels of selected circular RNAs (hsa_circRNA_103809 and hsa_circRNA_104700) were measured by real-time polymerase chain reaction in 170 paired colorectal cancer samples for validation. Statistical analyses were conducted to investigate the association between hsa_circRNA_103809 and hsa_circRNA_104700 expression levels and respective patient clinicopathological features. Receiver operating characteristic curve was constructed to evaluate the diagnostic values. Our results indicated that there were 125 downregulated and 76 upregulated circular RNAs in colorectal cancer tissues compared with normal tissues. We also first demonstrated that the expression levels of hsa_circRNA_103809 ( p < 0.0001) and hsa_circRNA_104700 ( p = 0.0003) were significantly lower in colorectal cancer than in normal tissues. The expression level of hsa_circRNA_103809 was significantly correlated with lymph node metastasis ( p = 0.021) and tumor-node-metastasis stage ( p = 0.011), and the expression level of hsa_circRNA_104700 was significantly correlated with distal metastasis ( p = 0.036). The area under receiver operating characteristic curves of hsa_circRNA_103809 and hsa_circRNA_104700 were 0.699 ( p < 0.0001) and 0.616 ( p < 0.0001), respectively. In conclusion, these results suggest that hsa_circRNA_103809 and hsa_circRNA_104700 may be potentially involved in the development of colorectal cancer and serve as potential biomarkers for the diagnosis of colorectal cancer.
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Circular RNAs (circRNAs) are a type of noncoding RNAs generated from back-splicing, which have been verified to mediate multiple tumorigenesis. With the development of high-throughput sequencing, massive circRNAs are discovered in tumorous tissue. However, the potential physiological effect of circRNAs in breast cancer is still unknown. The purpose of this study is to investigate the expression profile of circRNA in breast cancer tissue and explore the in-depth regulatory mechanism in breast cancer tumorigenesis. In the present study, we screened the circRNA expression profiles in breast cancer tissue using circRNA microarray analysis. Totally 1705 circRNAs were identified to be significantly aberrant. Among these dysregulated circRNAs, hsa_circ_0001982 was markedly overexpressed in breast cancer tissue and cell lines. Bioinformatics analysis predicted that miR-143 acted as target of hsa_circ_0001982, which was confirmed by Dual-luciferase reporter assay. Loss-of-function and rescue experiments revealed that hsa_circ_0001982 knockdown suppressed breast cancer cell proliferation and invasion and induced apoptosis by targeting miR-143. In summary, our study preliminarily investigates the circRNA expression in breast cancer tissue and explores the role of competing endogenous RNA (ceRNA) mechanism in the progression, providing a novel insight for breast cancer tumorigenesis.
Circular RNA
Competing Endogenous RNA
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