The Biogenesis, Functions, and Roles of circRNAs in Bladder Cancer.
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ABSTRACT:
SUBMITTER: Li C
PROVIDER: S-EPMC7245432 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
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Project description:Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5' caps and 3' poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients' survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.
| S-EPMC7780637 | 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.
| S-EPMC5972357 | biostudies-literature
Project description:The chemical modification of RNA is a newly discovered epigenetic regulation mechanism in cells and plays a crucial role in a variety of biological processes. N6-methyladenine (m6A) mRNA modification is the most abundant form of posttranscriptional RNA modification in eukaryotes. Through the development of m6A RNA sequencing, the relevant molecular mechanism of m6A modification has gradually been revealed. It has been found that the effect of m6A modification on RNA metabolism involves processing, nuclear export, translation and even decay. As the most common malignant tumour of the central nervous system, gliomas (especially glioblastoma) have a very poor prognosis, and treatment efficacy is not ideal even with the application of high-intensity treatment measures of surgery combined with chemoradiotherapy. Exploring the origin and development mechanisms of tumour cells from the perspective of tumour biogenesis has always been a hotspot in the field of glioma research. Emerging evidence suggests that m6A modification can play a key role in gliomas through a variety of mechanisms, providing more possibilities for early diagnosis and targeted therapy of gliomas. The aim of the present review is to focus on the research progress regarding the association between m6A modification and gliomas. And to provide a theoretical basis according to the currently available literature for further exploring this association. This review may provide new insights for the molecular mechanism, early diagnosis, histologic grading, targeted therapy and prognostic evaluation of gliomas.
| S-EPMC7500025 | biostudies-literature
Project description:Circular RNAs (circRNAs) are covalently linked single-stranded RNAs, compared to linear counterparts that are relatively abundant, conserved, stable, and specific. Previously, most studies have revealed that circRNAs function in gene expression processes and participate in the pathogenesis of cancers, cardiovascular diseases, and neurological diseases. With advances in biotechnology, more biological functions of circRNAs have been found in several signaling pathways that are related to tumorigenesis, immunity, and metabolism. Recently, many circRNAs have been reported to be expressed abnormally and play important roles in the progression of autoimmune diseases. Thus, circRNAs may not only serve as potential biomarkers but also act as immune regulators and offer potential opportunities for therapy. This review briefly introduces the properties as well as the functions of circRNAs in different stages of gene expression. In addition, this article summarizes the available knowledge about abnormally expressed circRNAs in different autoimmune diseases and discusses their potential roles in these diseases, which helps us understand their regulatory mechanisms and provides future research perspectives.
| S-EPMC6454857 | biostudies-literature
Project description:Circular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), have a covalently closed circular structure resulting from pre-mRNA back splicing via spliceosome and ribozymes. They can be classified differently in accordance with different criteria. As circRNAs are abundant, conserved, and stable, they can be used as diagnostic markers in various diseases and targets to develop new therapies. There are various functions of circRNAs, including sponge for miR/proteins, role of scaffolds, templates for translation, and regulators of mRNA translation and stability. Without m7G cap and poly-A tail, circRNAs can still be degraded in several ways, including RNase L, Ago-dependent, and Ago-independent degradation. Increasing evidence indicates that circRNAs can be modified by N-6 methylation (m6A) in many aspects such as biogenesis, nuclear export, translation, and degradation. In addition, they have been proved to play a regulatory role in the progression of various cancers. Recently, methods of detecting circRNAs with high sensitivity and specificity have also been reported. This review presents a detailed overview of circRNAs regarding biogenesis, biomarker, functions, degradation, and dynamic modification as well as their regulatory roles in various cancers. It's particularly summarized in detail in the biogenesis of circRNAs, regulation of circRNAs by m6A modification and mechanisms by which circRNAs affect tumor progression respectively. Moreover, existing circRNA detection methods and their characteristics are also mentioned.
| S-EPMC8393742 | biostudies-literature
Project description:Bladder cancer is one of the most common malignant tumors of the urogenital system with high morbidity and mortality worldwide. Early diagnosis and personalized treatment are the keys to successful bladder cancer treatment. Due to high postoperative recurrence rates and poor prognosis, it is urgent to find suitable therapeutic targets and biomarkers. Glycans are one of the four biological macromolecules in the cells of an organism, along with proteins, nucleic acids, and lipids. Glycans play important roles in nascent peptide chain folding, protein processing, and translation, cell-to-cell adhesion, receptor-ligand recognition, and binding and cell signaling. Glycans are mainly divided into N-glycans, O-glycans, proteoglycans, and glycosphingolipids. The focus of this review is the discussion of glycans related to bladder cancer. Additionally, this review also addresses the clinical value of glycans in the diagnosis and treatment of bladder cancer. Abnormal glycans are likely to be potential biomarkers for bladder cancer.
| S-EPMC7303958 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a new class of endogenous regulatory RNAs characterized by covalently closed cyclic structure lacking poly-adenylated tails, and are capable of regulating gene expression at transcription or post-transcription levels. Recently, plentiful circRNAs have been discovered in breast cancer and some circRNAs expression profiles are specifically involved in the triple-negative breast cancer (TNBC). TNBC is a type of malignant tumor defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. Considering its clinical characteristics of high invasion, metastasis, poor prognosis, and lack of effective response to conventional chemotherapies or targeted therapies, it could be a promosing option to discover specific circRNAs as new targets for TNBC treatment. Meanwhile, accumulating evidence has demonstrated that circRNAs are dysregulated in TNBC tissues and are correlated with clinicopathological features and prognosis of TNBC patients. Furthermore, looking for circRNAs with high specificity and sensitivity will provide a new opportunity for the early diagnosis, clinical treatment, and prognosis monitoring of TNBC. Herein, we reviewed the biogenesis, regulatory mechanisms, and biological functions of circRNAs in TNBC and summarized the relationship between circRNAs expression and the clinicopathology, diagnosis, and prognosis of patients with TNBC.
| S-EPMC7937293 | biostudies-literature
Project description:Exonic circular RNAs (ecircRNAs) in animal cells are generated by backsplicing, and the biogenesis of ecircRNAs is regulated by an array of RNA binding proteins (RBPs). HNRNPD is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles, and whether HNRNPD regulates the biogenesis of circRNAs remains unknown. In this study, we examine the role of HNRNPD in the biogenesis of ecircRNAs. The levels of ecircRNAs are primarily increased upon depletion of HNRNPD. HNRNPD preferentially binds to motifs enriched with A and U nucleotides, and the flanking introns of ecircRNAs tend to have more numbers and higher intensity of HNRNPD binding sites. The levels of mRNAs are generally not significantly altered in HNRNPD knockout cells. For a small set of genes, the circRNA:mRNA ratio is substantially affected, and the mRNA levels of some of these genes demonstrate a significant decrease in HNRNPD knockout cells. CDK1 is identified as a key gene modulated by HNRNPD in the context of circRNA biogenesis. HNRNPD suppresses the biogenesis of circCDK1 and favours the generation of CDK1 mRNA, and the CDK1 protein is a critical regulator of the cell cycle and apoptosis. HNRNPD can participate in cellular physiology, including the cell cycle and apoptosis, and plays roles in clear cell renal cell carcinoma (ccRCC) by modulating circRNA biogenesis and the mRNA levels of key genes, such as CDK1.
| S-EPMC11346550 | biostudies-literature
Project description:Background Exosome circRNAs (Exo-circRNAs) regulate cancer progression and intercellular crosstalk in the tumor microenvironment. However, their biological functions and potential clinical importance in colorectal cancer (CRC) remain unknown. Methods We used exoRBase 2.0 data to identify significant differentially expressed Exo-circRNAs (Exo-DEcircRNAs) in CRC patients and healthy individuals. The least absolute shrinkage and selector operation algorithm, support vector machine-recursive feature elimination, and multivariate Cox regression analyses were used to select candidate Exo-circRNAs and constructed a diagnostic model. Quantitative reverse transcription-polymerase chain reaction analysis was performed to confirm the expression of Exo-circRNAs in the serum samples of patients. Furthermore, we constructed an exosome circRNA-miRNA-mRNA network for CRC. Upregulated target mRNAs in the exosome competing endogenous RNA (Exo-ceRNA) network were used for functional and pathway enrichment analyses. We identified 22 immune cell types in CRC patients using CIBERSORT. Correlation analysis revealed the relationship between Exo-ceRNA networks and immune-infiltrating cells. The relationship between target mRNAs and immunotherapeutic response was also explored. Finally, using the Kaplan–Meier survival curve, a prognostic upregulated target mRNA was screened. We constructed a survival-related Exo-ceRNA subnetwork and explored the correlation between the Exo-ceRNA subnetwork and immune-infiltrating cells. Results The constructed diagnostic model had a high area under the curve (AUC) value in both the training and validation sets (AUC = 0.744 and AUC = 0.741, respectively). qRT-PCR confirmed that the Exo-circRNAs were differentially expressed in CRC serum samples. We constructed Exo-ceRNA networks based on the interactions among seven upregulated Exo-DEcircRNAs, eight differentially expressed miRNAs, and twenty-two differentially expressed mRNAs in CRC. Functional enrichment analysis revealed that the upregulated target mRNAs were significantly enriched in cytoskeletal motor activity and the PI3K-Akt signaling pathway. Co-expression analysis showed a significant correlation between the Exo-ceRNA networks and immune cells. The significant correlation was observed between target mRNAs and the immunotherapeutic response. Additionally, based on the prognostic upregulated target gene (RGS2), we constructed a survival-related Exo-ceRNA subnetwork (Exosome hsa_circ_0050334-hsa_miR_182_5p-RGS2). CIBERSORT results revealed that the Exo-ceRNA subnetwork correlated with M2 macrophages (P = 4.6e-07, R = 0.31). Conclusions Our study identified an Exo-diagnostic model, established Exo-ceRNA networks, and explored the correlation between Exo-ceRNA networks and immune cell infiltration in CRC. These findings elucidated the biological functions of Exo-circRNAs and their potential clinical implications.
| S-EPMC9339618 | biostudies-literature
Project description:PIWI-interacting RNA (piRNAs), once thought to be mainly functioning in germlines, are now known to play an essential role in somatic and cancerous tissues. Ping-pong cycle initiation and mitochondria-based phased production constitute the core of the piRNA biogenesis and these two processes are well conserved in mammals, including humans. By being involved in DNA methylation, histone marker deposition, mRNA degradation, and protein modification, piRNAs also contribute to carcinogenesis partly due to oncogenic stress-induced piRNA dysregulation. Also, piRNAs play important roles in cancer stemness, drug resistance, and tumor immunology. Results from liquid biopsy analysis of piRNA can be used in both cancer diagnoses and cancer prognoses. A combination of targeting piRNA with other therapeutic strategies could be groundbreaking cancer treatment.
| S-EPMC8278532 | biostudies-literature