circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1
Zhuoan ChengChengtao YuShaohua CuiHui WangHaojie JinCun WangBotai LiMeilin QinChen YangJia HeQiaozhu ZuoSiying WangJun LiuWeidong YeYuanyuan LvFangyu ZhaoMing YaoLiyan JiangWenxin Qin
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Abstract Circular RNAs (circRNAs) are identified as vital regulators in a variety of cancers. However, the role of circRNA in lung squamous cell carcinoma (LUSC) remains largely unknown. Herein, we explore the expression profiles of circRNA and mRNA in 5 paired samples of LUSC. By analyzing the co-expression network of differentially expressed circRNAs and dysregulated mRNAs, we identify that a cell cycle-related circRNA, circTP63 , is upregulated in LUSC tissues and its upregulation is correlated with larger tumor size and higher TNM stage in LUSC patients. Elevated circTP63 promotes cell proliferation both in vitro and in vivo. Mechanistically, circTP63 shares miRNA response elements with FOXM1. circTP63 competitively binds to miR-873-3p and prevents miR-873-3p to decrease the level of FOXM1, which upregulates CENPA and CENPB, and finally facilitates cell cycle progression.Keywords:
FOXM1
Competing Endogenous RNA
Circular RNA
Aim: Circular RNAs (circRNAs) with miRNA response elements (MREs) could function as competing endogenous RNA (ceRNA) in regulating gene expression. This study was carried out to identify the expression profile and role of circRNAs in endometriosis. Materials & methods: Microarray assay was performed in four paired ovarian endometriomas and eutopic endometrium, followed by quantitative real-time RT–PCR in 24 paired samples. Bioinformatical algorithms were used to predict MREs, as well as ceRNA and KEGG pathway analysis. Results: We identified 262 upregulated and 291 downregulated circRNAs, binding with 1225 MREs. The ceRNA network included 122 miRNAs and 137 mRNAs, which are involed in nine pathways. Conclusion: CircRNAs are differentially expressed in endometriosis, which might be related with pathogenesis of endometriosis.
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Circular RNA (circRNA), a type of non‑coding RNA, plays a regulatory role in biological processes. The special loop structure of circRNA makes it highly stable and specific in diseased tissues and cells, especially in tumors. Competing endogenous RNAs (ceRNAs) compete for the binding of microRNA (miRNA) at specific binding sites and thus regulate gene expression. ceRNAs play an important role in various diseases and are currently recognized as the most prominent mechanism of action of circRNAs. circRNAs can modulate the proliferation, migration, invasion and apoptosis of tumor cells through the ceRNA mechanism. With further research, circRNAs may serve as novel markers and therapeutic targets for ovarian cancer (OC). In the present review, the research progress of circRNAs as ceRNAs in OC was summarized, focusing on the effects of the circRNA/miRNA/mRNA axis on the biological functions of OC cells through mediating pivotal signaling pathways. The role of circRNAs in the diagnosis, prognostic assessment and treatment of OC was also discussed in the present review.
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BACKGROUND Little is known about epigenetic regulation of intracranial aneurysms (IAs). Circular non-coding RNAs (circRNAs) play crucial roles in cardiovascular diseases, but they have received scant research attention regarding their relationship with IAs. This study aimed to explore new pathological mechanisms of IA through circRNA expression profiles and to provide novel therapeutic strategies. MATERIAL AND METHODS The comprehensive circRNA and mRNA expression profiles were detected by RNA-Seq in human IA walls and superficial temporal arteries (STAs). The RNA-Seq findings were validated by qRT-PCR. GO and KEGG analyses indicated the functions of these circRNAs. A competing endogenous RNA (ceRNA) network was constructed to reveal the circRNA-miRNA-mRNA relationship. Two newly discovered circRNAs were further detected in peripheral blood of IA patients and healthy people to clarify their expression patterns in the periphery. RESULTS Many differentially expressed circRNAs are closely involved in immune/inflammatory response and cell adhesion/adherens junction. The novel circRNAs (hsa_circ_0072309 and hsa_circ_0008433) regulate DDR2 and MMP2, respectively, which are associated with SMC dysfunction and vascular injury through ceRNA. Moreover, we found differential expression of these 2 circRNAs in the peripheral blood of IA patients, and the expression pattern of hsa_circ_0072309 had central and peripheral consistency. CONCLUSIONS To the best of our knowledge, this is the first study to perform circRNA sequencing analysis of IAs. hsa_circ_0072309 and hsa_circ_0008433 are novel and pivotal circRNAs related to IAs. This study provides new insights into therapeutic targets and biomarkers for IA patients.
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Circular RNAs (circRNAs) have been recently proposed as hub molecules in various diseases, especially in tumours. We found that circRNAs derived from ribonuclease P RNA component H1 (RPPH1) were highly expressed in colorectal cancer (CRC) samples from Gene Expression Omnibus (GEO) datasets.We sought to identify new circRNAs derived from RPPH1 and investigate their regulation of the competing endogenous RNA (ceRNA) and RNA binding protein (RBP) networks of CRC immune infiltration.The circRNA expression profiles miRNA and mRNA data were extracted from the GEO and The Cancer Genome Atlas (TCGA) datasets, respectively. The differentially expressed (DE) RNAs were identified using R software and online server tools, and the circRNA-miRNA-mRNA and circRNA-protein networks were constructed using Cytoscape. The relationship between targeted genes and immune infiltration was identified using the GEPIA2 and TIMER2 online server tools.A ceRNA network, including eight circRNAs, five miRNAs, and six mRNAs, was revealed. Moreover, a circRNA-protein network, including eight circRNAs and 49 proteins, was established. The targeted genes, ENOX1, NCAM1, SAMD4A, and ZC3H10, are closely related to CRC tumour-infiltrating macrophages.We analysed the characteristics of circRNA from RPPH1 as competing for endogenous RNA binding miRNA or protein in CRC macrophage infiltration. The results point towards the development of a new diagnostic and therapeutic paradigm for CRC.
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Abstract Background Keloid is a dermal fibroproliferative disease with various etiologies and unclear pathogenesis. Recent studies have revealed that circular RNAs (circRNAs) exerted regulatory functions through a competing endogenous RNA (ceRNA) pathway in keloid progression. However, the expression profiles of circRNAs in keloid dermal tissues (KDTs) remain unknown. This study aimed to identify differentially expressed circRNAs (DECs) and genes (DEGs) in KDTs, as well as to investigate the potential biological functionsof circRNAs based on the circRNA-miRNA-mRNA ceRNA network. Results Through high-throughput RNA sequencing (RNA-seq), we revealed 3467 DEGs (865 up- and 2602 down-regulated) and 330 DECs (162 up- and 168 down-regulated) in KDTs. To reveal the functions of DECs preliminarily, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for the host genes. Further, the up- and down-regulated DECs-miRNAs-DEGs regulatory networks were constructed, respectively. The functional prediction for the target genes showed that the up-regulated ceRNA network was associated with extracellular matrix and multiple cellular functions. The down-regulated ceRNA network was enriched in cell-cell junction and other biological processes. Cytoscape was used to visualize each network's protein-protein interaction (PPI) network and identify hub genes. By quantitative Real-Time PCR (qRT-PCR), hsa_circ_0060927, hsa_circ_0071410, hsa_circ_0058092, hsa_circ_0002874, hsa_circ_0004682, hsa_circ_0072688, hsa_circ_0006401, and hsa_circ_0055954 were identified significantly up-regulated in KDTs. Within, hsa_circ_0072688, which was up-regulated both in KDTs and keloid dermal fibroblasts (KDFs), and located in the cytoplasm, might be a key circRNA and affect the progression of keloid by impacting extracellular matrix, cell adhesion, and cell apoptosis, etc. Conclusion This study not only filled a gap in the circRNA library of KDTs but also laid a foundation for probing the biological function of DECs in keloids. Hsa_circ_0072688 was thought to be a key circRNA and more experimental support is needed.
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Introduction: Intrahepatic cholangiocarcinoma (iCCA) is a heterogeneous entity with diverse etiologies, morphologies, and clinical outcomes, but our knowledge of its epidemiology and carcinogenesis is very limited. Materials and methods: The expression patterns of circRNAs were explored in iCCA tissues and corresponding adjacent normal ones, denoted by (iCCA) and (iCCAP), respectively, using high-throughput sequencing. Results: A total of 117 differential expressed (DE) circRNAs were identified. Based on the parental transcripts of circRNAs, these DE circRNAs were related to several important GO terms and were enriched in important pathways. Two circRNA-mediated ceRNA networks were constructed and many important metabolic pathways related to mRNAs were regulated by DE circRNAs via miRNAs. Conclusion: Our study revealed the DE circRNAs in the iCCA tissues compared with iCCAP ones, suggesting that circRNAs may play crucial roles in the pathogenesis of iCCA.
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Circular RNA (circRNA) is widely found in various species' cells.They have several characteristics including structural stability,high expression and expression in a tissue-specific manner.Recent studies have demonstrated that circRNA is a member of competing endogenous RNA (ceRNA).CircRNA regulate the expression of related RNA molecules via binding with target microRNA (miRNA) and play an important role in gene expression and regulation.The finding of circRNAs not only expand our understanding about eucaryon and ceRNA regulation network,but also indicate that circRNA might be a new biological marker for diagnosis and has good application prospects in drug development research,and disease diagnosis and treatment.Because current research on circRNA is still very few,a brief summary about circRNA is presented in this paper for further research.
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Circular RNAs (circRNAs) are connected at the 3′ and 5′ ends by exon or intron cyclization, forming a complete ring structure. circRNA is more stable and conservative than linear RNA and abounds in various organisms. In recent years, increasing numbers of reports have found that circRNA plays a major role in the biological functions of a network of competing endogenous RNA (ceRNA). circRNAs can compete together with microRNAs (miRNAs) to influence the stability of target RNAs or their translation, thus, regulating gene expression at the transcriptional level. circRNAs are involved in biological processes such as tumor cell proliferation, apoptosis, invasion, and migration as ceRNAs. circRNAs, therefore, represent promising candidates for clinical diagnosis and treatment. Here, we review the progress in studying the role of circRNAs as ceRNAs in tumors and highlight the participation of circRNAs in signal transduction pathways to regulate cellular functions.
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Recently, several studies have been conducted on circRNA (circular RNA). circRNA regulates gene expression and plays a vital role in the occurrence and development of various tumors. However, the role and mechanism of hsa_circ_0032683 in hepatocellular carcinoma (HCC) is not studied yet. In GEO (Gene Expression Omnibus) database, hsa_circ_0032683 expression was significantly lower in HCC tissues than in normal liver tissues. In vitro and in vivo functional tests revealed that hsa_circ_0032683 could inhibit HCC cells proliferation and promote their apoptosis. Mechanically, hsa_circ_0032683 primarily exists in the cytoplasm and competes with microRNA-338-5p (miR-338-5p) to regulate reticulon 4(RTN4). Our experiments revealed that hsa_circ_0032683 receded the proliferation ability of HCC via ceRNA (competing endogenous RNAs) mechanism, which provided potential biomarkers and therapeutic targets for HCC patients.Abbreviations: circRNAs: circular RNA; HCC: hepatocellular carcinoma; RTN4: reticulon 4; ceRNA: competing endogenous RNA; GEO: Gene Expression Omnibus; miRNA: microRNA; CSCD: Cancer-specific circRNA database; CRI: Circular RNA Interactome; TCGA: The Cancer Genome Atlas; qRT‐PCR: quantitative real‐time PCR; NEK9:NIMA-related kinase nine; CSMD1: CUB and Sushi multiple domains 1; Tob1: transducer of ERBB2, 1; miR: microRNA; sh: short hairpin; WT: wild type; MUT: mutant
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