circrna
212418999
Insights into the regulatory role of circRNA in angiogenesis and clinical implications.
Angiogenesis is the physiological process of new blood vessel formation from existing capillary vessels or posterior capillary veins. Its dysfunction could result in a number of diseases, such as cardiovascular diseases and cancer, contributing to death and disability worldwide. Circular RNAs (circRNAs) are a class of novel identified RNA molecules with a special covalent loop structure without a 5' cap and 3' tail, which can lead to novel back splicing or skipping events from precursor mRNAs. Accumulating evidence suggests that circRNA play critical roles in diseases; in particular, they are abundantly and abnormally expressed in angiogenesis related diseases. In this review, we describe the role of circRNA under pathological conditions, discuss the association between circRNA and angiogenesis, classify the regulatory mechanisms and suggest that circRNA can be used as potential therapeutic targets for angiogenesis related diseases under clinical evaluation.
Atherosclerosis
Yan Liu Yanyan Yang Zhibin Wang Xiuxiu Fu Xianming Chu Yonghong Li Qi Wang Xingqiang He M Li Kun Wang Jian-xun Wang Pei-Feng Li Tao Yu
53242236
Exosomal circRNA derived from gastric tumor promotes white adipose browning by targeting the miR 133/PRDM16 pathway
Cancer related cachexia is a metabolic syndrome characterized by a wasting disorder of adipose and skeletal muscle and is accompanied by body weight loss and systemic inflammation. The treatment options for cancer cachexia are limited, and the molecular mechanism remains poorly understood. Circular RNAs (circRNAs) are a novel family of endogenous noncoding RNAs that have been proposed to regulate gene expression in mammals. Exosomes are small vesicles derived from cells, and recent studies have shown that circRNAs are stable in exosomes. However, little is known about the biological role of circRNAs in exosomes. In our study, we showed that circRNAs in plasma exosomes have specific expression features in gastric cancer (GC) and ciRS 133 is linked with the browning of white adipose tissue (WAT) in GC patients. Exosomes derived from GC cells deliver ciRS 133 into preadipocytes, promoting the differentiation of preadipocytes into brown like cells by activating PRDM16 and suppressing miR 133. Moreover, knockdown of ciRS 133 reduced cancer cachexia in tumor implanted mice, decreasing oxygen consumption and heat production. Thus, exosome delivered circRNAs are involved in WAT browning and play a key role in cancer associated cachexia.
International journal of cancer
Haiyang Zhang Lei Zhu Ming Bai Ying Liu Yang Zhan Ting Deng Haiou Yang Wu Sun Xinyi Wang Kegan Zhu Qian Fan Jialu Li Guoguang Ying Yi Ba
203384393
Emerging roles of circRNA in formation and progression of cancer
Circular RNAs (circRNAs) are recently discovered as a special novel type of endogenous noncoding RNAs (ncRNAs) which form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. Recent research revealed that circRNAs can function as microRNA (miRNA) sponges, regulators of splicing and transcription, as well as interact with RNA binding proteins (RBPs) In this review, not only the function and mechanism, but also the experimental methods of circRNA are summarized. The summary of the current state of circRNA will help us in the discovery of novel biomarkers, the therapeutic targets and their potential significance in diagnosis and treatment of diseases. CircRNAs might play important roles in cancers especially in hepatocellular carcinoma, gastric carcinoma and colorectal cancer as well as serving as diagnostic or predictive biomarkers of some diseases and providing new treatments of diseases.
Journal of Cancer
Yuting Yin Jiali Long Qinglian He Yu-Ling Li Yanqiu Liao Peishan He Wei Zhu
58614355
CircRNA hsa_circRNA_101996 increases cervical cancer proliferation and invasion through activating TPX2 expression by restraining miR 8075
In recent years, circular RNAs have been shown to serve as essential regulators in several human cancers. Nevertheless, the function and mechanism of CircRNA in cervical cancer remain elusive. In the present study, we showed that hsa_circRNA_101996 was highly expressed in cervical cancer tissues compared with matched normal tissues by bioinformatics analysis. We showed that the expression level of hsa_circRNA_101996 in cervical cancer tissues was positively correlated with TNM stage, tumor size, and lymph node metastasis. Moreover, higher levels of hsa_circRNA_101996 were related to poor outcomes of cervical cancer patients. We found that knockdown of hsa_circRNA_101996 significantly inhibited the proliferation, cell cycle, migration, and invasion of cervical cancer cells. Mechanistically, we demonstrated that hsa_circRNA_101996 served as a sponge of miR 8075, which targeted TPX2 in cervical cancer cells. We showed that miR 8075 that was downregulated in cervical cancer tissues repressed cervical cancer cell proliferation, migration, and invasion. Furthermore, we validated that upregulation of TPX2 by hsa_circRNA_101996 mediated inhibition of miR 8075 contributed to cervical cancer proliferation, migration, and invasion. Taken together, our findings revealed a novel mechanism that hsa_circRNA_101996 miR 8075 TPX2 network promoted cervical cancer progression.
Journal of cellular physiology
Tiefang Song Aili Xu Zongfeng Zhang Fei Gao Lin Zhao Xiuhui Chen Jiayin Gao Xianchao Kong
203659620
CircRNA Cdr1as functions as a competitive endogenous RNA to promote hepatocellular carcinoma progression
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Recent years, circular RNA (circRNA) have been shown to exert vital functions in the pathological progressions of many diseases. A growing number of evidences have identified the representative function of exosomal circRNAs in the physiological state of donor cells, which further induces cellular responses after captured by recipient cells. However, the contributions of circRNAs to HCC remain largely unknown. In vitro and in vivo regulatory roles of circRNA Cdr1as in proliferative and migratory abilities of HCC were evaluated by CCK8, EdU, Transwell and tumourigenicity assays, respectively. Results showed circRNA Cdr1as was highly expressed in HCC cell lines and tissues. Overexpression of circRNA Cdr1as greatly accelerated HCC cells to proliferate and migrate. Mechanistically, we found that Cdr1as could promote the expression of AFP, a well known biomarker for HCC, by sponging miR 1270. Further studies showed exosomes extracted from HCC cells overexpressing circRNA Cdr1as accelerated the proliferative and migratory abilities of surrounding normal cells. In all, circRNA Cdr1as serves as a ceRNA to promote the progression of HCC. Meanwhile, it is directly transferred from HCC cells to surrounding normal cells via exosomes to further mediate the biological functions of surrounding cells.
Aging
Yang Su Xiurui Lv Wei Yin Lingling Zhou Yilin Hu Ang Zhou Fu-zhen Qi
20803305
Microarray is an efficient tool for circRNA profiling
Circular RNAs (circRNAs) are emerging as a new class of endogenous and regulatory noncoding RNAs in latest years. With the widespread application of RNA sequencing (RNA seq) technology and bioinformatics prediction, large numbers of circRNAs have been identified. However, at present, we lack a comprehensive characterization of all these circRNAs in interested samples. In this study, we integrated 87 935 circRNAs sequences that cover most of circRNAs identified till now represented in circBase to design microarray probes targeting back splice site of each circRNA to profile expression of those circRNAs. By comparing the circRNA detection efficiency of RNA seq with this circRNA microarray, we revealed that microarray is more efficient than RNA seq for circRNA profiling. Then, we found ~80 000 circRNAs were expressed in cervical tumors and matched normal tissues, and ~25 000 of them were differently expressed. Notably, many of these circRNAs detected by this microarray can be validated by quantitative reverse transcription polymerase chain reaction (RT qPCR) or RNA seq. Strikingly, as many as ~18 000 circRNAs could be robustly detected in cell free plasma samples, and the expression of ~2700 of them differed after surgery for tumor removal. Our findings provided a comprehensive and genome wide characterization of circRNAs in paired normal tissues and tumors and plasma samples from multiple individuals. In addition, we also provide a rich resource with 41 microarray data sets and 10 RNA seq data sets and strong evidences for circRNA expression in cervical cancer. In conclusion, circRNAs could be efficiently profiled by circRNA microarray to target their reported back splice sites in interested samples.
Briefings Bioinform.
Shasha Li Shuaishuai Teng Junquan Xu Guannan Su Yu Zhang Jianqing Zhao Suwei Zhang Haiyan Wang Wenyan Qin Zhi John Lu Yong Guo Qianyong Zhu Dong Wang
85531476
Extracellular Vesicles Long RNA Sequencing Reveals Abundant mRNA, circRNA, and lncRNA in Human Blood as Potential Biomarkers for Cancer Diagnosis.
BACKGROUND Extracellular vesicles (EVs) contain a rich cargo of different RNA species with specialized functions and clinical applications. However, the landscape and characteristics of extracellular vesicle long RNA (exLR) in human blood remain largely unknown. METHODS We presented an optimized strategy for exLR sequencing (exLR seq) of human plasma. The sample cohort included 159 healthy individuals, 150 patients with cancer (5 cancer types) and 43 patients with other diseases. Bioinformatics approaches were used to analyze the distribution and features of exLRs. Support vector machine algorithm was performed to construct the diagnosis classifier, and diagnostic efficiency was evaluated by ROC analysis. RESULTS More than 10000 exLRs, including mRNA, circRNA, and lncRNA, were reliably detected in each exLR seq sample from 1 2 mL of plasma. We observed that blood EVs contain a substantial fraction of intact mRNAs and a large number of assembling spliced junctions; circRNA was also enriched in blood EVs. Interestingly, blood exLRs reflected their tissue origins and the relative fractions of different immune cell types. Additionally, the exLR profile could distinguish patients with cancer from healthy individuals. We further showed that 8 exLRs can serve as biomarkers for hepatocellular carcinoma (HCC) diagnosis with high diagnostic efficiency in training [area under the curve (AUC) 0.9527; 95% CI, 0.9170 0.9883] validation cohort (AUC 0.9825; 95% CI, 0.9606 1) and testing cohort (AUC 0.9627; 95% CI, 0.9263 0.9991) CONCLUSIONS In summary, this study revealed abundant exLRs in human plasma and identified diverse specific markers potentially useful for cancer diagnosis.
Clinical chemistry
Yuchen Li Jing-Jing Zhao Shulin Yu Zhen Wang Xigan He Yonghui Su Tianan Guo Haoyue Sheng Jie Nan Chen Qiupeng Zheng Yan Li Weijie Guo Xiaohong Cai Guohai Shi Jiong Wu Lu Wang Peng Wang Xianghuo He Shenglin Huang
59339922
circRNA.33186 Contributes to the Pathogenesis of Osteoarthritis by Sponging miR 127 5p.
Osteoarthritis (OA) the most prevalent age related joint disorder, is characterized by chronic inflammation, progressive articular cartilage destruction, and subchondral bone sclerosis. Accumulating evidences indicate that circular RNAs (circRNAs) play a critical role in various diseases, but the function of circRNAs in OA remains largely unknown. Here we showed that circRNA.33186 was significantly upregulated in IL 1b) treated chondrocytes and in cartilage tissues of a destabilized medial meniscus (DMM) induced OA mouse model. Knockdown of circRNA.33186 increased anabolic factor (type II collagen) expression and decreased catabolic factor (MMP 13) expression. Knockdown of circRNA.33186 also promoted proliferation and inhibited apoptosis in IL 1b treated chondrocytes. Silencing of circRNA.33186 in vivo markedly alleviated DMM induced OA. Mechanistic study showed that circRNA.33186 directly binds to and inhibits miR 127 5p, thereby increasing MMP 13 expression, and contributes to OA pathogenesis. Taken together, our findings demonstrated a fundamental role of circRNA.33186 in OA progression and provide a potential drug target in OA therapy.
Molecular therapy the journal of the American Society of Gene Therapy
Zhi-bin Zhou Gao-xiang Huang Qiang Fu Bin Han Jiajia Lu Ai-min Chen Lei Zhu
133608834
Circbank: a comprehensive database for circRNA with standard nomenclature
ABSTRACT Circular RNAs (circRNAs) represent a new type of regulatory RNA which forms a covalently closed continuous loop from back splicing events, a process in which the downstream 5' splice site and the 3' splice site are covalently linked. Emerging evidence indicates that circRNAs exert a new layer of transcriptional and post transcriptional regulation of gene expression. However, there is no standard nomenclature of circRNA, although the study of circRNAs has exploded in the past few years. Here we present circbank (www.circbank.cn) a comprehensive database for human circRNAs, where a novel naming system of circRNAs based on the host genes of circRNAs was implemented. In addition to the new naming system, circbank collected other five features of circRNAs including the miRNA binding site, conservation of circRNAs, m6A modification of circRNAs, mutation of circRNAs and protein coding potential of circRNAs. Circbank is publicly available and allows users to query, browse and download circRNAs with all six features we provided, based on different search criteria. The database may serve as a resource to facilitate the research of function and regulation of circRNAs.
RNA biology
Ming Liu Qian Wang Jian Shen Burton B Yang Xiangming Ding
53789767
CircRNA ZNF609 functions as a competitive endogenous RNA to regulate FOXP4 expression by sponging miR 138 5p in renal carcinoma
Circular RNA (circRNA) play important roles in the pathological processes of many diseases. By analyzing the results of the GSE100186 chip, we found that the expression of circRNA ZNF609 (circ ZNF609) was significantly increased in renal cell carcinoma. Recently, there are studies showing that circ ZNF609 can regulate cell proliferation and invasion ability of various cells. In this study, we investigated whether circ ZNF609 may affect cell invasion and proliferation in renal carcinoma. Quantitative reverse transcription polymerase chain reaction was performed to detect the expression of circ ZNF609 in renal carcinoma cell lines and renal epithelial cells. The direct interaction between microRNA 138 5p (miR 138 5p) and forkhead box P4 (FOXP4) or circ ZNF609 was confirmed by luciferase reporter assay and RNA immunoprecipitation assay. We use Cell Counting Kit 8, 5 ethynyl 2' deoxyuridine, and Matrigel assays to assess the effect of miR 138 5p or circ ZNF609 on cell proliferation or invasion ability. And we found that circ ZNF609 is significantly increased in renal carcinoma cell lines. In addition, the high expression of circ ZNF609 promotes cell proliferation and invasion ability. In short, our current study reveals the role of the circ ZNF609/miR 138 5p/FOXP4 regulatory network in renal carcinoma and provides a new perspective for the pathogenesis of renal carcinoma.
Journal of cellular physiology
Yun-he Xiong Jiabin Zhang Chao Song