The expression profiles of circular RNAs and competing endogenous RNA networks in intrahepatic cholangiocarcinoma
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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.Keywords:
Competing Endogenous RNA
Circular RNA
Intrahepatic Cholangiocarcinoma
Pathogenesis
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.
Competing Endogenous RNA
Circular RNA
KEGG
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MicroRNA (miRNA) is an important type of non-coding RNAs with both physiological and pathological functions in human beings. Aberrant expression of miRNAs has been found in tumor tissues and the expression profile of certain groups of miRNAs is now emerging as bio-marker for cancer. It has been confirmed that miRNAs can exert oncogenic or tumor-suppressive functions through repressing the expression of their target genes which play different roles in tumorigenesis. The identification of oncogenic or tumor-suppressive miRNAs allows potential applications of these miRNAs as targets for cancer chemotherapy. In this review, we summarized the well-known cancer-related miRNAs reported in recent years and the roles they played in tumorigenesis and progression by targeting specific genes. Strategies developed to modulate the function or expression of the dysregulated miRNAs are also reviewed with recent examples illustrating their potential applications in cancer chemotherapy. Keywords: MicroRNA, oncogenic, tumor-suppressive, up-regulation, down-regulation, tumorigenesis, cancer chemotherapy.
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MicroRNA (miRNA ) 是在长度的 2123 核苷酸的小非编码的 RNA 分子的簇,它在 post-transcriptional 水平控制目标基因的表达式。最近的研究显示了 miRNA 在 carcinogenesis 起一个必要作用,例如影响房间生长,区别, apoptosis,和房间周期。现在,涉及 carcinogenesis 的 miRNA 的多重答应角色正在出现,并且 miRNA 仔细联系到 epithelialmesenchymal 转变(EMT ) 的进程,这被显示出,癌症干细胞(CSC ) 的规定,肿瘤侵略和移植的开发。miRNA 也充当稳定地在浆液表示的 biomarker 并且为各种各样的癌症的分子的目标治疗提供新目标。这评论的目的是在 carcinogenesis 说明 miRNA 的新角色并且在癌症加亮 miRNA 的新前景临床的申请,例如在血清学的诊断和分子目标的治疗学。
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Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous hepatobiliary tumor with poor prognosis, and it lacks reliable prognostic biomarkers and effective therapeutic targets. Long non-coding RNAs (lncRNAs) have been documented to be involved in the progression of various cancers. However, the role of lncRNAs in ICC remains largely unknown. In the present work, we used bioinformatics analysis to identify the differentially expressed lncRNAs in human ICC tissues, among which lncRNA-PAICC was found to be an independent prognostic marker in ICC. Moreover, lncRNA-PAICC promoted the proliferation and invasion of ICC cells. Mechanistically, lncRNA-PAICC acted as a competitive endogenous RNA (ceRNA) that directly sponged the tumor suppressive microRNAs miR-141-3p and miR-27a-3p. The competitive binding property was essential for lncRNA-PAICC to promote tumor growth and metastasis through activating the Hippo pathway. In summary, our results highlighted the important role of the lncRNA-PAICC-miR-141-3p/27a-3p-Yap1 axis in ICC, which offers a novel perspective on the molecular pathogenesis and may serve as a potential target for antimetastatic molecular therapies of ICC.
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Intrahepatic Cholangiocarcinoma
YAP1
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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.
Competing Endogenous RNA
Circular RNA
Intrahepatic Cholangiocarcinoma
Pathogenesis
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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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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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Abstract A new class of regulatory molecules known as microRNAs (miRNAs) is redefining our understanding of the molecular pathways associated with tumorigenesis. These miRNAs are small noncoding RNA (ncRNA) sequences with potent regulatory potential. The aberrant expression of miRNAs has been associated with the development of various tumors. It has been suggested that miRNAs can both regulate and act as tumor‐suppressor genes and oncogenes. Our understanding of the role of miRNAs in head and neck tumorigenesis is in its infancy. However, several recent studies have revealed extensive dysregulation of miRNA in head and neck tumors and have highlighted the potential of certain miRNAs to act as diagnostic and prognostic markers and targets for new therapeutic agents. The intent of this review is to discuss and summarize current findings that point to a significant role for miRNAs in head and neck tumorigenesis. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
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