Circular RNA in pancreatic cancer: a novel avenue for the roles of diagnosis and treatment.
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ABSTRACT:
SUBMITTER: Rong Z
PROVIDER: S-EPMC7806488 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Ovarian cancer (OC), an important cause of cancer-related death in women worldwide, is one of the most malignant cancers and is characterized by a poor prognosis. RNA-binding proteins (RBPs), a class of endogenous proteins that can bind to mRNAs and modify (or even determine) the amount of protein they can generate, have attracted great attention in the context of various diseases, especially cancers. Compelling studies have suggested that RBPs are aberrantly expressed in different cancer tissues and cell types, including OC tissues and cells. More specifically, RBPs can regulate proliferation, apoptosis, invasion, metastasis, tumorigenesis and chemosensitivity and serve as potential therapeutic targets in OC. Herein, we summarize what is currently known about the biogenesis, molecular functions and potential roles of human RBPs in OC and their prospects for application in the clinical treatment of OC.
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Project description:To analyze the diagnostic value of a circular RNA (circRNA), circ-LDLRAD3, in pancreatic cancer.Expression levels of circ-LDLRAD3 were tested in both cells and clinical samples; the latter included 30 paired pancreatic cancer tissues and adjacent non-tumorous tissues, 31 plasma samples from patients with pancreatic cancer, and 31 plasma samples from healthy volunteers. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to measure expression levels of circ-LDLRAD3 in cells and clinical samples; then, the relationship between clinicopathological factors of patient samples and expression of circ-LDLRAD3 in pancreatic cancer was analyzed. The diagnostic value of circ-LDLRAD3 was verified by receiver operating characteristic (ROC) curve analysis.Circ-LDLRAD3 was up-regulated in pancreatic cancer cell lines (P < 0.01), pancreatic cancer tissues (P < 0.01), and plasma samples from patients with pancreatic cancer (P < 0.01). High expression of circ-LDLRAD3 was significantly associated with venous invasion, lymphatic invasion, and metastasis. The area under the ROC curve of circ-LDLRAD3 alone or combination with CA19-9 was 0.67 and 0.87, respectively, with a sensitivity and specificity of 0.5738 (alone) and 0.7049 (alone), and 0.8033 (combination) and 0.9355 (combination), respectively.These data suggest that circ-LDLRAD3 may be a biomarker in the diagnosis of pancreatic cancer.
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Project description:BackgroundThe purpose of the study was to explore the precise parts of circ_0066147 (circular RNA [circRNA] scm-like with four mbt domains 1, circSFMBT1) in pancreatic cancer (PC) progression.MethodsRibonuclease R assay was used to confirm the stability of circ_0066147. circ_0066147, miR-326 and E2F transcription factor 2 (E2F2) expression levels was detected by quantitative reverse-transcription polymerase chain reaction or Western blot. Cell proliferation, apoptosis, migration and invasion abilities were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide, flow cytometry, wound-healing and transwell assays, respectively. Targeted relationships among circ_0066147, miR-326 and E2F2 were verified by the dual-luciferase reporter or RNA pull-down assay.Resultscirc_0066147 expression was upregulated in PC tissues and cells. circ_0066147 knockdown inhibited PC cell proliferation, migration, invasion and enhanced apoptosis in vitro, as well as weakened tumor growth in vivo. Mechanistically, circ_0066147 directly targeted miR-326 and circ_0066147 modulated E2F2 expression by miR-326. miR-326 mediated the regulation of circ_0066147 in PC cell behaviors in vitro. Furthermore, E2F2 was a functional target of miR-326 in modulating PC cell behaviors in vitro.Conclusioncirc_0066147 regulated PC malignant progression in part depending on the miR-326/E2F2 axis, illuminating circ_0066147 was a potential prognostic marker and therapeutic target for PC management.
| S-EPMC8142380 | biostudies-literature
Project description:Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in China. In recent years, therapies for oncogenedrivers and immune checkpoints have proved inspiring. Circular RNA (circRNA), which is a kind of RNA with covalent ring structure relating to stages and metastasis of cancer, has many special biological functions in physiological processes, diseases and so on. Thus, circRNA is expected to be a potential biomarker for cancer prediction and treatment in view of its high conservation and tissue-specific. However, function analysis and regulatory mechanism of circRNA in lung cancer come so far remains unclear and limited literatures are available. In this review, we highlight the research history, formation mechanism, biological function of circRNA and research progress in cancer, especially in lung cancer. We mean to provide theoretical evidences and new ideas for researches on circRNAs in lung cancer.
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Project description:Breast cancer is one of the most common cancers with the highest morbidity and mortality among women despite the treatment approaches have advanced including surgery, endocrine therapy and targeted therapy. Novel biomarkers are warranted to be discovered for the early detection, treatment and prognosis for breast cancer. CircRNA is a class of covalently closed single-stranded circular RNA molecules without free 5' or 3' end which makes them well expressed and more stable than their linear counterparts. In this review, we mainly discuss the oncogenic or anti-oncogenic roles of circRNAs can be utilized in the treatment and prognosis of breast cancer. A large number of circRNAs have shown great potential to function in carcinogenesis, metastasis or chemoresistance of breast cancer through transcriptional regulation of RNAs including miRNA and mRNA, in addition to their promise as stable biomarkers that can be used for monitoring breast cancer progression. However, the translation phenomenon of circRNAs in breast cancer and the diagnostic value of circRNAs in breast cancer requires further investigation for which the detection of circRNAs in plasma exosomes could be worthy of a try. Above all, engineered exosomes preloaded with engineered anti-oncogenic circRNAs are likely to provide a novel direction in the personal medicine of breast cancer.
| S-EPMC6684920 | biostudies-literature
Project description:Pancreatic cancer (PaCa) is the fourth leading cause of cancer-related deaths in the United States, and the vast majority of these malignancies are pancreatic ductal adenocarcinomas (PDAC), but there is still a lack of early detection biomarkers for PaCa. Unlike linear RNAs, circRNAs form covalently closed continuous loops and can act as mammalian gene regulators. They may be diagnostic or predictive biomarkers for some tumors, also be novel potential therapeutic targets in different diseases. This review focuses on (1) the biogenesis of circRNAs, RNA binding proteins (RBPs) and complementary sequences of circRNAs; (2) the characteristics of circRNAs which allow them to interact with miRNAs; (3) the roles of circRNAs playing in the regulation of gene expression, cell behavior and cancer, and their potential role as novel biomarkers and therapeutic targets in pancreatic cancer.
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Project description:Currently, despite the advances in individualized treatment, breast cancer still remains the deadliest form of cancer in women. Diagnostic, prognostic, and therapy-predictive methods are mainly based on the evaluation of tumor tissue samples and are aimed to improve the overall therapeutic level. Therefore, the exploration of a series of circulating biomarkers, which serve as the information source of tumors and could be obtained by peripheral blood samples, represents a high field of interest. Apart from classical biomarkers, exosomes, which are nanovesicles, are emerging as an accessible and efficient source of cell information. The purpose of this review is to summarize the peculiarities of the presently available breast cancer exosomal biomarkers; the review also provides the prediction of a multitude of potential target genes of exosomal microRNAs using 4 databases.
| S-EPMC6373987 | biostudies-literature
Project description:The regulatory roles of circular RNAs (circRNAs) in cancer are attracting increasing attention. The aim of the present study was to explore the roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) using microarray data. The circRNA and microRNA (miRNA) microarray data were downloaded from Gene Expression Omnibus. A total of 256 differentially expressed circRNAs were obtained by analyzing the circRNA microarray data from 26 pairs of PDAC and adjacent normal tissues. Differentially expressed miRNAs were analyzed using a dataset of 6 PDAC tissues and 5 non-neoplastic pancreas samples (GSE43796); 20 differentially expressed miRNAs were detected. circRNA/miRNA interactions were predicted between differentially expressed circRNAs and miRNAs using miRanda and RNAhybrid algorithms and 51 circRNA/miRNA interactions were obtained. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using gene symbols of differentially expressed circRNAs demonstrated that 41 circRNAs were enriched in 17 pathways. Subnetworks that were associated with apoptosis or proliferation were extracted from the 17 pathways and a new network was constructed using Cytoscape software, which identified that mitogen-activated protein kinase, PI3K/AKT and WNT/β-catenin signaling pathways may be associated with PDAC development. In conclusion, 256 differentially expressed circRNAs and 20 differentially expressed miRNAs were identified in PDAC tissues compared with normal tissues; the circRNA/miRNA interactions and the networks of KEGG pathways provided a global view of the function of these differentially expressed circRNAs and miRNAs.
| S-EPMC6676441 | biostudies-literature
Project description:Cervical cancer (CC) is one of the most threatening diseases in women. Circular RNAs (circRNAs) have been reported to be cancer hallmarks, but typical circRNAs in CC were rarely indicated. Through high-throughput sequencing in CC and normal cervix tissues, circYPEL2 (hsa_circ_0005600) was proposed as a candidate circRNA. CircYPEL2 exhibited significantly high expression in CC tissue and strong stability in CC cell lines. Furthermore, knockdown and overexpression of circYPEL2 indicated the potential involvement in CC proliferation, migration and invasion. Finally, the downstream regulatory genes of circYPEL2 were investigated by knockdown experiment in CC cell lines with high-throughput sequencing. In summary, our work identified circYPEL2 as a potential biomarker for clinical research of cervical cancer.
| S-EPMC8774301 | biostudies-literature
Project description:Background N6-methyladenosine (m6A) is the most abundant modification of RNA in eukaryotic cells and play critical roles in cancer. While most related studies focus on m6A modifications in linear RNA, transcriptome-wide profiling and exploration of m6A modification in circular RNAs in cancer is still lacking. Methods For the detection of m6A modification in circRNAs, we developed a new bioinformatics tools called Circm6A and applied it to the m6A-seq data of 77 tissue samples from 58 individuals with pancreatic ductal adenocarcinoma (PDAC). Results Circm6A performs better than the existing circRNA identification tools, which achieved highest F1 score among these tools in the detection of circRNAs with m6A modifications. By using Circm6A, we identified a total of 8807 m6A-circRNAs from our m6A-seq data. The m6A-circRNAs tend to be hypermethylated in PDAC tumor tissues compared with normal tissues. The hypermethylated m6A-circRNAs were associated with a significant gain of circRNA-mRNA coexpression network, leading to the dysregulation of many important cancer-related pathways. Moreover, we found the cues that hypermethylated m6A-circRNAs may promote the circularization and translation of circRNAs. Conclusions These comprehensive findings further bridged the knowledge gaps between m6A modification and circRNAs fields by depicting the m6A-circRNAs genomic landscape of PDAC patients and revealed the emerging roles played by m6A-circRNAs in pancreatic cancer. Circm6A is available at https://github.com/canceromics/circm6a. Supplementary Information The online version contains supplementary material available at 10.1186/s13073-021-01002-w.
| S-EPMC8605608 | biostudies-literature