Research Progress of Circular RNA in Gastrointestinal Tumors.
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ABSTRACT:
SUBMITTER: Fang N
PROVIDER: S-EPMC8082141 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Owing to the success of linear mRNA coronavirus disease 2019 (COVID-19) vaccines, biopharmaceutical companies and research teams worldwide have attempted to develop more stable circular RNA (circRNA) vaccines and have achieved some preliminary results. This review aims to summarize key findings and important progress made in circRNA research, the in vivo metabolism and biological functions of circRNAs, and research progress and production process of circRNA vaccines. Further, considerations regarding the quality control of circRNA vaccines are highlighted herein, and the main challenges and problem-solving strategies in circRNA vaccine development and quality control are outlined to provide a reference for circRNA vaccine-related research.
| S-EPMC9878156 | biostudies-literature
Project description:AimsTo explore the expression of circular RNA (circRNA) in gastrointestinal stromal tumors.BackgroundGastrointestinal stromal tumors (GIST) are mainly distributed in the stomach and small intestine. Recently, it has been verified that circular RNA (circRNA) has an important function in the regulation of GIST. Nevertheless, detailed investigations of circRNA-miRNA-mRNA regulatory networks in GIST are lacking.ObjectiveTo analyze the gastrointestinal stromal tumor circRNA-miRNA-mRNA network, assessing the effect of circle RNA in gastrointestinal stromal tumors.MethodAll the differential circRNAs and mRNAs were obtained from Gene Expression Omnibus (GEO) microarray data (GSE131481 and GSE147303, GSE131481, and GSE13861). Furthermore, a circRNA-miRNA-mRNA network was established. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to reveal the correlation between the functions of signaling pathways and target genes. The hub genes of protein-protein interaction (PPI) network and cytoHubba were also defined. Quantitative real-time PCR (qRT-PCR) was used to measure the expression levels of hsa-circ-0002917 (circTBC1D4), hsa-miR-590-5p (miR-590-5p), and PLN.ResultsPPI network and Cytoscape showed that ATP1A2, PLN, KCNMA1, and SCNN1B were four central DEGs. GO analysis results revealed that DEGs were involved in negative management of myocardial contraction, regulation of myocardial cell contraction, ethanol oxidation, cellular potassium ion homeostasis, and relaxation of cardiac muscle, and KEGG analysis showed that major DEGs were with cGMP-PKG signaling pathway. Moreover, we obtained two pairs of axes, namely, hsa-circ-0039216/hsa-miR-338-3p/ATP1A2 and hsa-circ-0002917/hsa-miR-590-5p/PLN. The target of TBC1D4 is miR-590-5p, and miR-590-5p increased after knocking down TBC1D4. Moreover, PLN was the target of miR-590-5p, and miR-590-5p exerts antitumor effects by reducing PLN.ConclusionsIn this study, we constructed a circRNA-miRNA-mRNA management network interrelated with GIST and researched the potential roles of circRNA. Moreover, we discovered a new molecular landmarker for the prediction, diagnosis, and therapy of patients.
| S-EPMC9155966 | biostudies-literature
Project description:AbstractIn recent years, the diagnosis and treatment of gastrointestinal stromal tumors (GISTs) of the small intestine have been a hot topic due to their rarity and non-specific clinical manifestations. With the development of gene and imaging technology, surgery, and molecular targeted drugs, the diagnosis and treatment of GISTs have achieved great success. For a long time, radical resection was prioritized to treat GISTs of the small intestine. At present, preoperative tumor staging is a novel treatment for unresectable malignant tumors. In addition, karyokinesis exponent is the sole independent predictor of progression-free survival of GISTs. The DNA, miRNA, and protein of exosomes have also been found to be biomarkers with prognostic implications. The research on the treatment of GISTs has become a focus in the era of precision medicine, ushering in the use of standardized, normalized, and individualized treatment.
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Project description:With completing the whole genome sequencing project, awareness of lncRNA further deepened. The growth arrest-specific transcript 5 (GAS5) was initially identified in growth-inhibiting cells. GAS5 is a lncRNA (long non-coding RNA), and it plays a crucial role in various human cancers. There are small ORFs (open reading frames) in the exons of the GAS5 gene sequence, but they do not encode functional proteins. In addition, GAS5 is also the host gene of several small nucleolar RNAs (snoRNA). These snoRNAs are believed to play a suppressive role during tumor progression by methylating ribosomal RNA (rRNA). As a result, GAS5 expression levels in tumor tissues are significantly reduced, leading to increased malignancy, poor prognosis, and drug resistance. Recent studies have demonstrated that GAS5 can interact with miRNAs by base-pairing and other functional proteins to inhibit their biological functions, impacting signaling pathways and changing the level of intracellular autophagy, oxidative stress, and immune cell function in vivo. In addition, GAS5 participates in regulating proliferation, invasion, and apoptosis through the above molecular mechanisms. This article reviews the recent discoveries on GAS5, including its expression levels in different tumors, its biological behavior, and its molecular regulation mechanism in human cancers. The value of GAS5 as a molecular marker in the prevention and treatment of cancers is also discussed.
| S-EPMC9273967 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a large class of endogenous RNA that form a covalently closed continuous loop without 5' or 3' tails and are diffusely expressed in mammalian cells. Through the development of high-throughput sequencing, microarray, and bioinformatics analyses, recent studies have shown that the expression of circRNAs is dysregulated in human tumor tissues and cells, as well as in the blood of patients, and closely correlates with the development of tumors. circRNAs can regulate the progression of tumors through various mechanisms. An increasing number of studies have shown that circRNAs may play critical roles in the early diagnosis, targeted therapy, and prognostic prediction of cancer as biomarkers or therapeutic targets. This review briefly describes the definitions and functions of circRNAs, and the main content includes the most recent progress in research into their function, regulation, and clinical relevance to bladder, renal, and prostate cancers. We also provide some novel ideas regarding the treatment of these diseases.
| S-EPMC7045884 | biostudies-literature
Project description:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and have gained considerable research and treatment interest, especially in the last two decades. GISTs are driven by mutations commonly found in the KIT gene and less commonly in the platelet-derived growth factor receptor alpha gene, BRAF gene and succinate dehydrogenase gene. GISTs behave in a spectrum of malignant potential, and both the tumor size and mitotic index are the most commonly used prognostic criteria. Whilst surgical resection can offer the best cure, targeted therapy in the form of tyrosine kinase inhibitors (TKIs) has revolutionized the management options. As the first-line TKI, imatinib offers treatment for advanced and metastatic GISTs, adjuvant therapy in high-risk GISTs and as a neoadjuvant agent to downsize large tumors prior to resection. The emergence of drug resistance has altered some treatment options, including prolonging the first-line TKI from 1 to 3 years, increasing the dose of TKI or switching to second-line TKI. Other newer TKIs, such as sunitinib and regorafenib, may offer some treatment options for imatinib-resistant GISTs. New molecular targeted therapies are being evaluated, such as inhibitors of BRAF, heat shock protein 90, glutamine and mitogen-activated protein kinase signaling, as well as inhibitors of apoptosis proteins antagonist and even immunotherapy. This editorial review summarizes the recent research trials and potential treatment targets that may influence our future patient-specific management of GISTs. The current guidelines in GIST management from Europe, North America and Asia are highlighted.
| S-EPMC5526756 | biostudies-literature
Project description:The circadian clock refers to the inherent biological rhythm of an organism, which, is accurately regulated by numerous clock genes. Studies in recent years have reported that the abnormal expression of clock genes is ubiquitous in common abdominal malignant tumors, including liver, colorectal, gastric and pancreatic cancer. In addition, the abnormal expression of certain clock genes is closely associated with clinical tumor parameters or patient prognosis. Studies in clock genes may expand the knowledge about the mechanism of occurrence and development of tumors, and may provide a new approach for tumor therapy. The present study summarizes the research progress in this field.
| S-EPMC5661368 | biostudies-other
Project description:Gastrointestinal stromal tumor (GIST) originates from interstitial cells of Cajal (ICCs) in the myenteric plexus of the gastrointestinal tract. Most GISTs arise due to mutations of KIT and PDGFRA gene activation, encoding the receptor tyrosine kinase (RTK). The clinical use of the RTK inhibitor imatinib has significantly improved the management of GIST patients; however, imatinib resistance remains a challenge. The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is a critical survival pathway for cell proliferation, apoptosis, autophagy and translation in neoplasms. Constitutive autophosphorylation of RTKs has an impact on the activation of the PI3K/AKT/mTOR pathway. In several preclinical and early-stage clinical trials PI3K/AKT/mTOR signaling inhibition has been considered as a promising targeted therapy strategy for GISTs. Various inhibitory drugs targeting different parts of the PI3K/AKT/mTOR pathway are currently being investigated in phase I and phase II clinical trials. This review highlights the progress for PI3K/AKT/mTOR-dependent mechanisms in GISTs, and explores the relationship between mTOR downstream signals, in particular, eukaryotic initiation factors (eIFs) and the development of GISTs, which may be instrumental for identifying novel therapeutic targets.
| S-EPMC7602170 | biostudies-literature
Project description:Motivation:Circular RNAs (circRNAs) originate through back-splicing events from linear primary transcripts, are resistant to exonucleases, are not polyadenylated, and have been shown to be highly specific for cell type and developmental stage. CircRNA detection starts from high-throughput sequencing data and is a multi-stage bioinformatics process yielding sets of potential circRNA candidates that require further analyses. While a number of tools for the prediction process already exist, publicly available analysis tools for further characterization are rare. Our work provides researchers with a harmonized workflow that covers different stages of in silico circRNA analyses, from prediction to first functional insights. Results:Here, we present circtools, a modular, Python-based framework for computational circRNA analyses. The software includes modules for circRNA detection, internal sequence reconstruction, quality checking, statistical testing, RNA binding protein enrichment screenings, differential exon RNase R resistance, and circRNA-specific primer design. Circtools supports researchers with visualization options and data export into commonly used formats. Availability:Circtools is available via github.com/dieterich-lab/circtools and circ.tools under GPLv3.0. Supplementary information:Supplementary data are available at Bioinformatics online.
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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.
| S-EPMC5972357 | biostudies-literature