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.

https://www.tandfonline.com/doi/pdf/10.1080/15476286.2019.1600395

Circbank: a comprehensive database for circRNA with standard nomenclature.

CircRNAs and cancer: Biomarkers and master regulators.

Most genetic information is expressed as, and transacted by, proteins. Yet, less than 2% of the human genome actually codes for proteins, prompting a search for functions for the other 98% of the genome, once considered to be mostly “junk DNA.” Transcription is pervasive, however, and high-throughput sequencing has identified tens of thousands of distinct RNAs generated from the non—protein—coding portion of the genome ( 1 ). These so-called noncoding RNAs vary in length, but like protein-coding RNAs, appear to be linear molecules with 5′ and 3′ termini, reflecting the defined start and end points of RNA polymerase on the DNA template. But do all RNAs have to be linear?

A Circuitous Route to Noncoding RNA

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.

/pdf/emerging-roles-of-circrna-in-formation-and-progression-of-4tc6294w2i.pdf

Emerging roles of circRNA in formation and progression of cancer.

Colorectal cancer (CRC) is a common hereditary tumor that is often fatal Its pathogenesis involves multiple genes, including circular RNAs (circRNAs) Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research

/pdf/comprehensive-landscape-and-future-perspectives-of-circular-15el0nvpyz.pdf

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer

The aim of the present study was to screen colorectal cancer (CRC) tissue and adjacent tissue for differences in circular RNA (circRNA) expression, to analyze the related miRNAs and messenger RNAs (mRNAs), and to investigate the circRNA expression in CRC and its function. The circRNA expression profile was generated using CapitalBio microarray technology. The differentially expressed circRNAs were identified with GeneSpring 12.5 software. Subsequently, the related mRNAs of the differentially expressed circRNAs were annotated with the molecule annotation system (MAS) 3.0, and the diseases, pathways and functional enrichment analysis of these mRNAs were performed using the KEGG orthology-based annotation system (KOBAS) 3.0. In addition, the target miRNAs of differentially expressed circRNAs were screened using the miRanda algorithm. The circRNA/miRNA network was constructed for the top 8 most significant differentially expressed circRNAs with Cytoscape software 3.4.0. A total of 10,245 differentially expressed circRNAs were identified, including 6,264 upregulated ones, and 3,981 downregulated ones. The related mRNAs were enriched in 462 KEGG diseases, 411 FunDO, 669 NHGRI GWAS catalog, and 845 OMIM; and 1,334 Reactomes, 281 KEGG pathways, 117 PANTHER and 193 BioCyc; and 11,606 Gene Ontology (GO) terms. A total of 133 circRNA/miRNA pairs were involved in the circRNA/miRNA network. hsa_circ_0126897_CBC1 may be a potential biomarker for CRC, and the cell cycle was closely associated with the occurrence and development of CRC.

/pdf/screening-potential-biomarkers-for-colorectal-cancer-based-23s5xrtn77.pdf

Screening potential biomarkers for colorectal cancer based on circular RNA chips

miR-1184 regulates the proliferation and apoptosis of colon cancer cells via targeting CSNK2A1.

The aim of the present study was to investigate the mechanism of metastasis in colorectal cancer (CRC) using microRNA (miRNA) and mRNA expression profiles. The mRNA and miRNA expression profiles of the GSE2509 and GSE56350 datasets were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified using the limma software package. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs. The predicted target genes associated with the DEMs were identified using the miRWalk database and the enrichment analysis was conducted using the clusterProfiler package. The miRNA-gene molecular interaction network was visualized using the Cytoscape software platform. A total of 544 DEGs and 42 DEMs were identified. DEGs were annotated in 320 GO terms and 11 KEGG pathways. Overall, 366 miRNA-gene pairs were identified and the miRNA-gene network was visualized. Furthermore, the predicted target genes were mainly classified in 12 pathways. The results of the present study suggest that fibronectin type III domain-containing 3B, cysteine rich transmembrane BMP regulator 1 and forkhead box J2 may be potential therapeutic and prognostic targets of metastatic CRC. In addition, pathways in cancer, the Wnt signaling pathway and extracellular matrix-receptor interaction may play a critical role in CRC metastasis.

https://www.spandidos-publications.com/10.3892/ol.2017.7044/download

Exploration of the mechanism of colorectal cancer metastasis using microarray analysis

Introduction It has been reported that lncRNA AGAP2-AS1 promotes the development of gastric cancer, lung cancer and breast cancer. This study aimed to investigate the role of AGAP2-AS1 in colon cancer. Methods A total of 66 patients with colon cancer were enrolled. RT-qPCR was performed to detect the differential expression of AGAP2-AS1 in tumor tissues and adjacent normal tissues. To test the interaction between AGAP2-AS1 and LINC-PINT in colon cancer, overexpression vector or inhibitor of AGAP2-AS1 and LINC-PINT were transfected into RKO and HCT 116 cells. CCK-8 assay was used to detect cell proliferation. Transwell assays were performed to evaluate cell migration and invasion. The expression of p-LATS1, p-YAP and nuclear YAP were detected by Western blot and immunofluorescence. Results The expression of AGAP2-AS1 was upregulated in colon cancer tissues compared with that in adjacent normal tissues, and the expression of AGAP2-AS1 in colon cancer tissues was not significantly affected by tumor stages. In addition, we found that the expression of LINC-PINT was downregulated in colon cancer tissues compared with that in adjacent normal tissues and had a reverse correlation with the expression of AGAP2-AS1 in colon cancer tissues. Moreover, overexpression of AGAP2-AS1 downregulated the expression of LINC-PINT, and overexpression of LINC-PINT also altered the expression of AGAP2-AS1 in colon cancer cells. Inhibition of AGAP2-AS1 upregulated the expression of LINC-PINT, and inhibition of LINC-PINT promoted the expression levels of AGAP2-AS1 in colon cancer cells. Furthermore, overexpression of AGAP2-AS1 could increase the proliferation, invasion and migration of colon cancer cells, while overexpression of LINC-PINT could attenuate the effects of overexpression of AGAP2-AS1 on the proliferation, migration and invasion of colon cancer cells. We also found that AGAP2-AS1 promoted colon cancer cell proliferation, migration and invasion through the Hippo signaling. Conclusion Upregulated expression of AGAP2-AS1 promoted proliferation, invasion and migration in colon cancer by forming a negative feedback loop with LINC-PINT.

/pdf/lncrna-agap2-as1-promotes-cancer-cell-proliferation-40li1xxlxs.pdf

LncRNA AGAP2-AS1 Promotes Cancer Cell Proliferation, Migration and Invasion in Colon Cancer by Forming a Negative Feedback Loop with LINC-PINT

Colorectal cancer (CRC) ranks the 3rd in cancer types globally. Long noncoding RNAs (lncRNAs) are related to the initiation and progression of CRC. The current study plans to reveal the action of rhabdomyosarcoma 2-associated transcript (RMST) in CRC. The results show that RMST is downregulated in CRC specimens and cell lines relative to normal specimens and a fetal normal colon cell line (FHC), respectively. Elevation of RMST represses cell proliferation and colony formation and induces cell apoptosis in CRC cells. Bioinformatic analysis reveals a binding site in RMST for miR-27a-3p. The direct association between RMST and miR-27a-3p is confirmed by dual luciferase reporter assay, RNA pull-down assay, and real time-quantitative polymerase chain reaction (RT-qPCR). miR-27a-3p is upregulated in CRC tumor specimens relative to normal specimens, and there is a negative correlation between RMST and miR-27a-3p in CRC tumor specimens. In addition, the effects of RMST overexpression are weakened by the elevation of miR-27a-3p. RMST and retinoid X receptor (RXRα) share the same complementary site with miR-27a-3p. The direct association between RXRα and miR-27a-3p is confirmed by RNA pull-down assay, RT-qPCR and western blot analysis. Overexpression of RMST induces RXRα expression and inactivates the Wnt signaling pathway by decreasing β-catenin levels in CRC cells. Collectively, our findings reveal a pivotal role of RMST in regulating miR-27a-3p/RXRα axis and counteracting Wnt signaling pathway during the progression of CRC.

lncRNA RMST suppresses the progression of colorectal cancer by competitively binding to miR-27a-3p/RXRα axis and inactivating Wnt signaling pathway

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