scholarly journals Exosomal circRNAs: new players in the field of cholangiocarcinoma

2019 ◽  
Vol 133 (21) ◽  
pp. 2239-2244 ◽  
Author(s):  
Corentin Louis ◽  
Matthis Desoteux ◽  
Cédric Coulouarn
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Human Tumor ◽  
Direct Interaction ◽  
Circular Rna ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Non Invasive ◽  
Tumor Tissues

Abstract Cholangiocarcinoma (CCA) is a deadly cancer worldwide associated with limited therapeutic options. A recent study published in Clinical Science by Wang and colleagues [Clin. Sci. (2019) 133(18), 1935–1953] brought new perspectives to CCA management and therapy by focusing on circular RNAs (circRNAs). CircRNAs belong to an emerging class of functional non-coding RNAs (ncRNAs) regulating numerous biological processes. Notably, circRNAs have been associated with cancer onset and progression, although reports in CCA are very limited so far. In this work, the expression of circular RNA circ-0000284 (aka circHIPK3) was specifically elevated in CCA cell lines, human tumor tissues and plasma exosomes. Gain and loss of function approaches were performed to better understand the molecular mechanisms regulated by circ-0000284. Notably, the authors evaluated the role of circ-0000284 as a microRNA (miRNA) sponge. By prediction analysis and functional tests, a direct interaction was demonstrated with miR-637 that targets lymphocyte antigen-6 E (LY6E). Increased expression of circ-0000284 was associated with enhanced migration, invasion and proliferation of CCA cell lines. Interestingly, exosomal-mediated circ-0000284 was reported to exhibit pro-oncogenic effects on surrounding normal cells. Altogether, these data highlight circRNAs not only as new players in CCA pathogenesis but also as promising molecules for innovative non-invasive biomarkers, as circRNAs are enriched and stable in exosomes. Further investigations on extracellular vesicles should provide the necessary tools to improve CCA diagnosis, and move toward targeted-therapies.

scholarly journals Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Yanshuo Han ◽  
Hao Zhang ◽  
Ce Bian ◽  
Chen Chen ◽  
Simei Tu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Human Life ◽  
Abdominal Aortic Aneurysms ◽  
Circular Rna ◽  
Aortic Aneurysms ◽  
Current Evidence ◽  
Circular Rnas ◽  
Regulatory Pathways ◽  
Abdominal Aortic

Abdominal aortic aneurysms (AAAs) have posed a great threat to human life, and the necessity of its monitoring and treatment is decided by symptomatology and/or the aneurysm size. Accumulating evidence suggests that circular RNAs (circRNAs) contribute a part to the pathogenesis of AAAs. circRNAs are novel single-stranded RNAs with a closed loop structure and high stability, having become the candidate biomarkers for numerous kinds of human disorders. Besides, circRNAs act as molecular “sponge” in organisms, capable of regulating the transcription level. Here, we characterize that the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. In the present work, studies on the biosynthesis, bibliometrics, and mechanisms of action of circRNAs were aims comprehensively reviewed, the role of circRNAs in the AAA pathogenic mechanism was illustrated, and their potential in diagnosing AAAs was examined. Moreover, the current evidence about the effects of circRNAs on AAA development through modulating endothelial cells (ECs), macrophages, and vascular smooth muscle cells (VSMCs) was summarized. Through thorough investigation, the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. The results demonstrated that circRNAs had the application potential in the diagnosis and prevention of AAAs in clinical practice. The study of circRNA regulatory pathways would be of great assistance to the etiologic research of AAAs.

scholarly journals Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Stage ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

scholarly journals CircMYOF triggers progression and facilitates glycolysis via the VEGFA/PI3K/AKT axis by absorbing miR-4739 in pancreatic ductal adenocarcinoma

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Dandan Zheng ◽  
Xianxian Huang ◽  
Juanfei Peng ◽  
Yanyan Zhuang ◽  
Yuanhua Li ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Circular Rna ◽  
Ductal Adenocarcinoma ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Competing Endogenous Rna ◽  
Rnase R

AbstractEmerging evidence has demonstrated that circular RNAs (circRNAs) take part in the initiation and development of pancreatic ductal adenocarcinoma (PDA), a deadly neoplasm with an extremely low 5-year survival rate. Reprogrammed glucose metabolism is a key feature of tumour development, including PDA. In this research, we evaluated the role of circRNAs in reprogrammed glucose metabolism in PDA. RNA sequencing under various glucose incubation circumstances was performed. A new circMYOF was identified. Sanger sequencing and RNase R treatment confirmed its circular RNA characteristics. Real-time PCR indicated that it was highly expressed in PDA clinical specimens and cell lines. Gain-of- and loss-of-function assays showed that circMYOF induced progression in PDA. Mechanistically, RNA pull-down and luciferase reporter experiments elucidated that circMYOF, as a competing endogenous RNA for miR-4739, facilitated glycolysis via the VEGFA/PI3K/AKT pathway. Taken together, our findings indicate that circMYOF may work as a desirable biomarker and therapeutic target for PDA patients.

scholarly journals Circular RNA circHIPK3 Promotes Cell Metastasis through miR-637/STAT3 Axis in Osteosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zhongyue Huang ◽  
Chunyan Yuan ◽  
Huijie Gu ◽  
Xiangyang Cheng ◽  
Kaifeng Zhou ◽  
...  
Keyword(s):  
Cell Lines ◽  
Normal Cell ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Cell Line ◽  
Diagnosis And Prognosis ◽  
Promising Therapeutic Target ◽  
Cell Metastasis

Recent studies have suggested that circular RNAs play an important role in the progression of various cancers. However, few studies have revealed the great value of circRNAs in the diagnosis and prognosis prediction of osteosarcoma (OS). In this study, we performed experiments with the human OS cell lines and the results showed that the expression of circHIPK3 in OS cell lines was significantly upregulated compared to that in the normal cell line. In addition, the results showed that circHIPK3 could promote the migration, invasion, and growth of OS cells. Furthermore, miR-637 was identified as a target of circHIPK3, while STAT3 was targeted by miR-637. circHIPK3 could promote STAT3 expression via interacting with miR-637 in OS cells. In conclusion, our research uncovered an important role of the circHIPK3/miR-637/STAT3 pathway in the migration and invasion of OS cells and suggested that circHIPK3 may be a prognostic marker and a promising therapeutic target for OS.

scholarly journals Identification of circular RNA hsa_circ_0044556 and its effect on the development and progression of colorectal cancer

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Stage ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Node Metastasis

Abstract Background Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNAs in the development and progression of colorectal cancer (CRC) remains unclear. Methods First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines. Results hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression. Conclusion hsa_circ_0044556 promoted the development and progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

scholarly journals Circular RNA circ-CCAC1 Facilitates Adrenocortical Carcinoma Cell Proliferation, Migration, and Invasion through Regulating the miR-514a-5p/C22orf46 Axis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wei Li ◽  
Rengong Liu ◽  
Dongmei Wei ◽  
Wei Zhang ◽  
Heyan Zhang ◽  
...  
Keyword(s):  
Cell Lines ◽  
Adrenocortical Carcinoma ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Loss Of Function ◽  
Tissue Samples ◽  
Tissue Specimens

Adrenocortical carcinoma (ACC) is a rare but clinically aggressive endocrine malignancy. Circular RNAs (circRNAs) were found to play key roles in tumorigenesis. In the current study, we aimed to investigate the functions and mechanisms of a novel circRNA, circ-CCAC1, in ACC cells. circ-CCAC1 expression levels in ACC tissue specimens and cell lines were evaluated by RT-qPCR. Kaplan-Meier analysis was applied to explore the relationship between circ-CCAC1 and patients’ prognosis. Cell counting kit-8 (CCK-8), colony formation, acridine orange/ethidium bromide (AO/EB) double fluorescence staining, and Transwell assays were performed to evaluate the functions of circ-CCAC1 in ACC cells. Bioinformatics analysis and a dual-luciferase reporter assay were utilized to explore the mechanisms of circ-CCAC1. As a result, circ-CCAC1 was overexpressed in ACC tissue samples and cell lines and correlated with poor prognosis. Gain- and loss-of-function tests demonstrated that circ-CCAC1 acted as an oncogene in ACC. What is more, circ-CCAC1 enhanced C22orf46 expression by sponging miR-514a-5p in ACC cells. A rescue assay illustrated that circ-CCAC1 facilitated ACC progression through miR-514a-5p/C22orf46 signaling. To sum up, we identified a novel circRNA, circ-CCAC1, which may be used as a potential therapeutic target for ACC.

scholarly journals Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

2020 ◽  
Author(s):  
Liang Jing ◽  
Junhui Wu ◽  
Xiaocheng Tang ◽  
Min Ma ◽  
Fei Long ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Tumor Stage ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

scholarly journals A novel circFMN2 promotes tumor proliferation in CRC by regulating the miR-1182/hTERT signaling pathways

2019 ◽  
Vol 133 (24) ◽  
pp. 2463-2479 ◽  
Author(s):  
Yongchao Li ◽  
Changfeng Li ◽  
Ruisi Xu ◽  
Yun Wang ◽  
Dandan Li ◽  
...  
Keyword(s):  
Cell Lines ◽  
Molecular Mechanisms ◽  
Direct Interaction ◽  
Chromosome 1 ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Central Component ◽  
Reporter System

Abstract Background: Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with colorectal cancer (CRC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for CRC from the aspect of circRNA–microRNA (miRNA)–mRNA interaction. Methods: We investigated the expression of circRNAs in five paired CRC tissues and adjacent non-tumor tissues by microarray analysis. Differentially expressed circRNAs were identified between CRC tissues and non-cancerous matched tissues. We focused on hsa_circ_0005100, which is located on chromosome 1 and derived from FMN2, and thus we named it as circFMN2. The expression of circFMN2 was detected in 88 CRC tissues and cell lines by quantitative real-time PCR. Functional assays were performed to evaluate the effects of circFMN2 on proliferation in vitro, and on tumorigenesis in vivo. The relationship between circFMN2 and miR-1182 was confirmed by luciferase reporter assay. Results: circFMN2 was found to be significantly up-regulated in CRC tissues and cell lines. Moreover, knockdown of circFMN2 significantly inhibited cell proliferation and migration in vitro. Bioinformatics analysis predicted that there is a circFMN2/miR-1182/hTERT axis in CRC progression. Dual-luciferase reporter system validated the direct interaction of circFMN2, miR-1182, hTERT. Western blot verified that inhibition of circFMN2 decreased hTERT expression. Importantly, we demonstrated that circFMN2 was up-regulated in serum exosomes from CRC patients. Conclusion: In conclusion, circFMN2 is a central component linking circRNAs to progression of CRC via an miR-1182/hTERT axis.

scholarly journals Circular RNA mmu_circ_0005019 inhibits fibrosis of cardiac fibroblasts and reverses electrical remodeling of cardiomyocytes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Wu ◽  
Chengying Li ◽  
Bin Xu ◽  
Ying Xiang ◽  
Xiaoyue Jia ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cardiac Fibroblasts ◽  
Circular Rna ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Candidate Target ◽  
Paired Control ◽  
Reporter Assays ◽  
And Migration

Abstract Background Circular RNA (circRNA) have been reported to play important roles in cardiovascular diseases including myocardial infarction and heart failure. However, the role of circRNA in atrial fibrillation (AF) has rarely been investigated. We recently found a circRNA hsa_circ_0099734 was significantly differentially expressed in the AF patients atrial tissues compared to paired control. We aim to investigate the functional role and molecular mechanisms of mmu_circ_0005019 which is the homologous circRNA in mice of hsa_circ_0099734 in AF. Methods In order to investigate the effect of mmu_circ_0005019 on the proliferation, migration, differentiation into myofibroblasts and expression of collagen of cardiac fibroblasts, and the effect of mmu_circ_0005019 on the apoptosis and expression of Ito, INA and SK3 of cardiomyocytes, gain- and loss-of-function of cell models were established in mice cardiac fibroblasts and HL-1 atrial myocytes. Dual-luciferase reporter assays and RIP were performed to verify the binding effects between mmu_circ_0005019 and its target microRNA (miRNA). Results In cardiac fibroblasts, mmu_circ_0005019 showed inhibitory effects on cell proliferation and migration. In cardiomyocytes, overexpression of mmu_circ_0005019 promoted Kcnd1, Scn5a and Kcnn3 expression. Knockdown of mmu_circ_0005019 inhibited the expression of Kcnd1, Kcnd3, Scn5a and Kcnn3. Mechanistically, mmu_circ_0005019 exerted biological functions by acting as a miR-499-5p sponge to regulate the expression of its target gene Kcnn3. Conclusions Our findings highlight mmu_circ_0005019 played a protective role in AF development and might serve as an attractive candidate target for AF treatment.

scholarly journals Hsa_circ_0005273 facilitates breast cancer tumorigenesis by regulating YAP1-hippo signaling pathway

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Xuehui Wang ◽  
Changle Ji ◽  
Jiashu Hu ◽  
Xiaochong Deng ◽  
Wenfang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Hippo Signaling ◽  
Hippo Signaling Pathway ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs), a novel class of endogenous RNAs, have shown to participate in the development of breast cancer (BC). Hsa_circ_0005273 is a circRNA generated from several exons of PTK2. However, the potential functional role of hsa_circ_0005273 in BC remains largely unknown. Here we aim to evaluate the role of hsa_circ_0005273 in BC. Methods The expression level of hsa_circ_0005273 and miR-200a-3p were examined by RT-qPCR in BC tissues and cell lines. The effect of knocking down hsa_circ_0005273 in BC cell lines were evaluated by examinations of cell proliferation, migration and cell cycle. In addition, xenografts experiment in nude mice were performed to evaluate the effect of hsa_circ_0005273 in BC. RNA immunoprecipitation assay, RNA probe pull-down assay, luciferase reporter assay and fluorescence in situ hybridization were conducted to confirm the relationship between hsa_circ_0005273, miR-200a-3p and YAP1. Results Hsa_circ_0005273 is over-expressed in BC tissues and cell lines, whereas miR-200a-3p expression is repressed. Depletion of hsa_circ_0005273 inhibited the progression of BC cells in vitro and in vivo, while overexpression of hsa_circ_0005273 exhibited the opposite effect. Importantly, hsa_circ_0005273 upregulated YAP1 expression and inactivated Hippo pathway via sponging miR-200a-3p to promote BC progression. Conclusions Hsa_circ_0005273 regulates the miR-200a-3p/YAP1 axis and inactivates Hippo signaling pathway to promote BC progression, which may become a potential biomarker and therapeutic target.

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