scholarly journals Expression Profiling Identifies Circular RNA Signature in Hepatoblastoma

2018 ◽  
Vol 45 (2) ◽  
pp. 706-719 ◽  
Author(s):  
Bai-Hui Liu ◽  
Bin-Bin Zhang ◽  
Xiang-Qi Liu ◽  
Shan Zheng ◽  
Kui-Ran Dong ◽  
...  
Keyword(s):  
Cell Function ◽  
Cyclic Compound ◽  
Normal Liver ◽  
Circular Rna ◽  
Fine Tuning ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Promising Target

Background/Aims: Hepatoblastoma is the most common malignant pediatric liver cancer. circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of circRNAs in hepatoblastoma is still unknown. Methods: Circular RNA microarray was conducted to identify hepatoblastoma-related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in hepatoblastoma. MTT assays, Ki67 staining, and Transwell assays were conducted to clarify the role of circRNA in hepatoblastoma in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in hepatoblastoma cell. Results: 869 differentially expressed circRNAs were identified between hepatoblastoma and adjacent normal liver samples, including 421 up-regulated circRNAs and 448 down-regulated circRNAs. The significant enriched GO term of hepatoblastoma-related circRNAs in biological process, cellular component, and molecular function were “chromosome organization”, “cytoplasm”, and “organic cyclic compound binding”. Tight junction signaling pathway was ranked the Top 1 potentially affected by circRNA-mediated regulatory network. circ_0015756 was significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. circ_0015756 silencing decreased hepatoblastoma cell viability, proliferation, and invasion in vitro. circ_0015756 acted as miR-1250-3p sponge to regulate hepatoblastoma cell function. Conclusions: circRNAs are involved in the pathogenesis of hepatoblastoma. circ_0015756 is a promising target for the prognosis, diagnosis, and treatment of hepatoblastoma.

scholarly journals Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1389-1398 ◽  
Author(s):  
Lili Zhu ◽  
Tingting Ren ◽  
Zixin Zhu ◽  
Mingliang  Cheng ◽  
Qiuju Mou ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Circular Rna ◽  
Fine Tuning ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
G1 Arrest

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis.

scholarly journals Comprehensive Circular RNA Profiling Reveals the Regulatory Role of the CircRNA-0067835/miR-155 Pathway in Temporal Lobe Epilepsy

2018 ◽  
Vol 51 (3) ◽  
pp. 1399-1409 ◽  
Author(s):  
Guo-Hua Gong ◽  
Feng-Mao An ◽  
Yu Wang ◽  
Ming Bian ◽  
Di Wang ◽  
...  
Keyword(s):  
Temporal Lobe Epilepsy ◽  
Temporal Lobe ◽  
Circular Rna ◽  
Fine Tuning ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
G1 Arrest ◽  
Rna Profiling

Background/Aims: Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown. Methods: Circular RNA microarray was conducted to identify TLE-related circRNAs. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in TLE in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in TLE cell. Results: 586 differentially expressed circRNAs were identified between TLE and the control tissues. The expression of circRNA-0067835 was significantly down-regulated in tissues and plasma from TLE patients. Lower circRNA-0067835 correlated to increased seizure frequency, HS, and higher Engel’s score. Overexpression of circRNA-0067835 observably decreased SH-SY5Y cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated refractory epilepsy progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with TLE.

scholarly journals Circular RNA circRPPH1 promotes breast cancer progression via circRPPH1-miR-512-5p-STAT1 axis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yixiang Huang ◽  
Wenfang Zheng ◽  
Changle Ji ◽  
Xuehui Wang ◽  
Yunhe Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Gene Expression Omnibus ◽  
Circular Rnas ◽  
In Vivo Experiments

AbstractBreast cancer (BC) is one of the most fatal diseases among women all over the world. Non-coding RNAs including circular RNAs (circRNAs) have been reported to be involved in different aspects during tumorigenesis and progression. In this study, we aimed to explore the biological functions and underlying mechanism of circRPPH1 in BC. Candidate circRNAs were screened in dataset GSE101123 from Gene Expression Omnibus (GEO) database and a differentially expressed circRNA, circRPPH1, was discovered in BC. CircRPPH1 expression was higher in the cancerous tissue compared to paired adjacent tissue. Further in vitro and in vivo experiments indicated that circRPPH1 acted as an oncogene in BC. In addition, circRPPH1 was mainly localized in cytoplasm and played the role of miR-512-5p sponge. By sequestering miR-512-5p from the 3′-UTR of STAT1, circRPPH1 inhibited the suppressive role of miR-512-5p, stabilized STAT1 mRNA in BC and finally affected BC progression. In conclusion, these findings indicated that circRPPH1 acted as an oncogene and regulated BC progression via circRPPH1-miR-512-5p-STAT1 axis, which might provide a potential therapeutic target for BC treatment.

scholarly journals The Potential Role of hsa_circ_0005505 in the Rupture of Human Intracranial Aneurysm

2021 ◽  
Vol 8 ◽  
Author(s):  
Xin Chen ◽  
Shuzhe Yang ◽  
Junhua Yang ◽  
Qingyuan Liu ◽  
Maogui Li ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Intracranial Aneurysm ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Intracranial Aneurysms ◽  
Circular Rna ◽  
Circular Rnas ◽  
Ruptured Intracranial Aneurysms

Objective: Recently, abundant number of studies have revealed many functions of circular RNAs in multiple diseases, however, the role of circular RNA in the rupture of human intracranial aneurysm is still unknown. This study aims to explore the potential functions of circular RNA in the rupture of human intracranial aneurysms.Methods: The differentially expressed circular RNAs between un-ruptured intracranial aneurysms (n = 5) and ruptured intracranial aneurysms (n = 5) were analyzed with the Arraystar human circRNAs microarray. Quantitative real-time PCR (qPCR) was used to verify the results of the circRNA microarray. The role of circular RNA in intracranial aneurysm rupture was assessed in vitro. MTT assay, CCK-8 assay, Caspase3/7 assay, assay of cell apoptosis and Celigo wound healing was conducted to evaluate the relationship between circular RNA and the rupture of human intracranial aneurysms.Results: A total of 13,175 circRNA genes were detected. Among them 63 circRNAs upregulated and 54 circRNAs downregulated significantly in ruptured intracranial aneurysms compared with un-ruptured intracranial aneurysms (p < 0.05 Fold Change > 1.5). Five upregulated circRNAs were selected for further study (hsa_circ_0001947, hsa_circ_0043001, hsa_circ_0064557, hsa_circ_0058514, hsa_circ_0005505). The results of qPCR showed only hsa_circ_0005505 significantly upregulated (p < 0.05). The expression of hsa_circ_0005505 was higher in ruptured intracranial aneurysm tissues. And our in vitro data showed that hsa_circRNA_005505 promotes the proliferation, migration and suppresses the apoptosis of vascular smooth muscle cell.Conclusion: This study revealed an important role of hsa_circ_0005505 in the proliferation, migration and apoptosis of vascular smooth muscle cell, and indicated that hsa_circ_0005505 may associate with the pathological process of intracranial aneurysms.

scholarly journals Circular RNA circASPM Promotes the Progression of Glioblastoma by Acting as a Competing Endogenous RNA to Regulate miR-130b–3p/E2F1 Axis

2020 ◽  
Author(s):  
Dianqi Hou ◽  
Zhenlin Wang ◽  
Haimeng Li ◽  
Juan Liu ◽  
Yaohua Liu ◽  
...  
Keyword(s):  
Western Blotting ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Primary Malignancy ◽  
Rna Immunoprecipitation ◽  
Western Blotting Assay

Abstract background: Glioblastoma Multiform (GBM) is the primary malignancy with the highest incidence and worst prognosis in the adult CNS. Circular RNAs (circRNAs) are a novel and widely diverse class of endogenous non-coding RNAs that can promote or inhibit gliomagenesis. Our study aimed to explore the role of circASPM in GBM and its molecular mechanism.Methods: Levels of circASPM, miR-130b-3p and E2F1 were determined by quantitative real-time PCR (qRT-PCR) or western blotting assay. MTS, Edu, neurospheres formation and extreme limiting dilution assays were used to detect the tumorigenesis and proliferation of GSCs in vitro. The interactions between miR-130b-3p and circASPM or E2F1 was demonstrated via qPCR, western blotting, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Xenograft experiments was used to analyze tumor growth in vivo.Results: CircASPM was overexpressed in GBM and could promote the tumorigenesis and proliferation of GSCs both in vitro and in vivo. Mechanistically, circASPM up-regulated the expression of E2F1 in GSCs via miR-130b-3p sponging. We furtherly demonstrated that circAPSM could promote the GSCs proliferation via E2F1 up-regulating. Therefore, our study identified a novel circRNA and its possible mechanism in the development and tumorigenesis of GBM.Conclusions: CircASPM can promote GBM progression via regulating miR-130b-3p/E2F1 axis, suggesting that circAPSM could provide an effective biomarker for GBM diagnosis and prognostic evaluation and possibly being used for molecular targeted therapy.

scholarly journals Chronic Stress-Induced Gene Changes In Vitro and In Vivo: Potential Biomarkers Associated With Depression and Cancer Based on circRNA- and lncRNA-Associated ceRNA Networks

2021 ◽  
Vol 11 ◽  
Author(s):  
Ting Zhou ◽  
Mingming Li ◽  
Zhijun Xiao ◽  
Jian Cai ◽  
Weiwei Zhao ◽  
...  
Keyword(s):  
Stress Hormones ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Mild Stress ◽  
And Control ◽  
Whole Transcriptome ◽  
Potential Biomarkers

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) have been considered as biomarkers or regulators in many diseases. However, the exact role of circRNA- or lncRNA-mediated competing endogenous RNA (ceRNA) networks in the modulation of depression pathogenesis-relevant processes is not clear. In this study, we profiled whole transcriptome in depression patients’ blood samples via microarray analysis. As a result, a total of 340 circRNAs, 398 lncRNAs, 206 miRNAs, and 92 mRNAs were differentially expressed between the depression and control groups. Then, we constructed ceRNA networks according to the differentially expressed genes (DEGs). Using bioinformatics analysis, 89 pairs of circRNA-ceRNA and 49 pairs of lncRNA-ceRNA networks were obtained. Since depression is a broad and heterogeneous condition that is known as promoter for many chronic diseases including cancer, so we further dug out 28 circRNAs, 61 lncRNAs, 26 miRNAs, and 29 mRNAs that are associated with cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were significantly enriched in cancer-related signaling pathways such as MAPK, Wnt, IL-17, Ras, and PI3K-Akt. Genes involved in the above pathways such as S100A9, GATA2, SRFP5, SLC45A3, NTRK1, FRZB, has_circ_0014221, has_circ_0014220, and has_circ_0087100 were dysregulated in various cancer cell lines by stress hormones induced. HDC, GATA2, SLC45A3, and NTRK1 were downregulated in tumor-bearing mice subjected to chronic unpredictable mild stress (CUMS). LncRNA-mediated ceRNA network validation showed that overexpression of miR-4530 declined HDC level. Our findings highlight the potential circRNA- and lncRNA-mediated ceRNA regulatory mechanisms in the pathogenesis of depression and as potential biomarkers in depression cancer comorbidity through the pathways of IL-17 or histidine metabolism.

scholarly journals The novel role of circular RNA ST3GAL6 on blocking gastric cancer malignant behaviors through autophagy regulated by the FOXP2/MET/mTOR axis

2021 ◽  
Author(s):  
Penghui Xu ◽  
Xing Zhang ◽  
Jiacheng Cao ◽  
Jing Yang ◽  
Zetian Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Circular Rna ◽  
Circular Rnas ◽  
The Novel ◽  
Transcriptional Inhibition ◽  
And Migration ◽  
Induced Apoptosis

Abstract Gastric cancer (GC) ranks third in motality among all cancers worldwide. Circular RNAs (circRNAs) play essential roles in the malignant progression and metastasis of gastric cancer. As a transcription factor, FOXP2 is involved in the progression of many tumours. However, the regulation and association between circRNAs and FOXP2 remain to be discovered. In our study, CircST3GAL6 was significantly depressed in GC tissues and cells. circST3GAL6 overexpression inhibited the proliferation, invasion and metastasis of GC cells in vitro and in vivo. Importantly, circST3GAL6 overexpression induced apoptosis and promote autophagy in GC cells. Furthermore, we found that circST3GAL6 sponged miR-300 and subsequently regulated FOXP2. We further revealed that FOXP2 suppressed the activation of the Met/AKT/mTOR axis, a classic pathway that regulates autophagy-mediated proliferation and migration. In summary, our findings revealed that circST3GAL6 functions as a tumour suppressor through the miR-300/FOXP2 axis in GC, regulates apoptosis and autophagy through FOXP2-mediated transcriptional inhibition of the MET axis and may be a biomarker for GC treatment.

scholarly journals The profile analysis of circular RNAs in human placenta of preeclampsia

2018 ◽  
Vol 243 (14) ◽  
pp. 1109-1117 ◽  
Author(s):  
Wenbo Zhou ◽  
Huiyan Wang ◽  
Xian Wu ◽  
Wei Long ◽  
Fangxiu Zheng ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Human Placenta ◽  
Profile Analysis ◽  
Placental Tissue ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Qrt Pcr ◽  
Potential Biomarker

A total of 70 pregnant women were recruited for this study, including 35 early onset preeclampsia (PE) and 35 normal pregnant women. By RNA sequencing, the circular RNA (circRNAs) in placenta were identified. Differentially expressed circRNAs were bioinformatics analyzed with gene ontology, Kyoto Encyclopedia of Genes and Genomes, and circRNA–miRNA interaction prediction. Quantitative real time polymerase chain reaction(qRT-PCR) assay was used to verify the results. Compared with the normal pregnant women, there were 49 circRNAs differentially expressed in the placental tissue of PE women, including two circRNAs were up-regulated and 47 were down-regulated. Ten differentially expressed circRNAs were selected for validation by qRT-PCR, among which results of three circRNAs, circRNA_3286, circRNA_5593, and circRNA_3800, were consistent with the sequencing. According to the bioinformatic prediction, we speculate that these circRNAs may be involved in some cellular regulatory functions in PE through their targeted miRNAs. We also evaluated the expression of circRNA_3286 in plasma to be used as a potential biomarker for PE; in vitro Transwell assay shown transfected with si-circ-3286 significantly reduced invasion in HTR8/Svneo cells. In conclusion, we displayed a preliminary landscape of circRNA differential expression in PE and discussed their possible regulatory mechanisms. This study revealed a new insight into the molecular mechanism of PE. Impact statement The abnormal expression of many regulatory factors may be involved in the development of PE. circRNAs are proved to have a series of important biological functions; however, reports about circRNA and PE are rare. In this work, we evaluated the profile analysis of circRNAs in human placenta of PE by RNA-seq and found some newly differentially expressed circRNAs which might be involved in PE. Combined with bioinformatics analysis, their possible functions were preliminarily discussed.

scholarly journals Circular RNA hsa_circ_0000073 Enhances Osteosarcoma Cells Malignant Behavior by Sponging miR-1252-5p and Modulating CCNE2 and MDM2

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhijing Ren ◽  
Qinqin Yang ◽  
Jiajia Guo ◽  
Haifeng Huang ◽  
Bo Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Malignant Tumor ◽  
Cell Function ◽  
Circular Rna ◽  
Tumor Promoter ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Novel Target

Objective: An increasing number of studies have demonstrated that circular RNAs (circRNAs) are involved in tumor progression. However, the role of hsa_circ_0000073 in osteosarcoma (OS) is still not fully elucidated.Methods: Quantitative reverse transcription-polymerase chain reaction or Western blot was used to detect the gene expression. GeneChip analysis, bioinformatics, luciferase reporter, and RNA immunoprecipitation assays were adopted to predict and verify the relationships between genes. Counting Kit-8 Assay, clone formation assay, wound-healing assay, transwell assays, cell cycle assays, and in vivo tumorigenesis were used to evaluate cell function.Results: hsa_circ_0000073 was highly expressed in OS cell lines and could promote OS progression, including proliferation, migration, invasion, and cell cycle in vitro as well as tumorigenesis in vivo. Mechanically, hsa_circ_0000073 could readily downregulate the expression of CCNE2 and MDM2 through miR-1252-5p. Rescue experiments validated miR-1252-5p mimics, or CCNE2/MDM2 short hairpin RNA could reverse the hsa_circ_0000073 overexpressing-induced impairment of malignant tumor behavior.Conclusion: hsa_circ_0000073 functions as a tumor promoter in OS to increase malignant tumor behavior through sponging miR-1252-5p and regulating CCNE2 and MDM2 expression, which could be a novel target for OS therapy.

scholarly journals Differentially Expressed Circular RNA Profile in an Intracranial Aneurysm Group Compared with a Healthy Control Group

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yonggang Ma ◽  
Baoqing Zhang ◽  
Dong Zhang ◽  
Shuo Wang ◽  
Maogui Li ◽  
...  
Keyword(s):  
Intracranial Aneurysm ◽  
Profile Analysis ◽  
Circular Rna ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Control Group ◽  
Expression Profile Analysis ◽  
Healthy Control ◽  
Polymerase Chain

Objective. Intracranial aneurysm (IA) is a fatal disease owing to vascular rupture and subarachnoid hemorrhage. Much attention has been given to circular RNAs (circRNAs) because they may be potential biomarkers for many diseases, but their mechanism in the formation of IA remains unknown. Methods. circRNA expression profile analysis of blood samples was conducted between patients with IA and controls. Overall, 235 differentially expressed circRNAs were confirmed between IA patients and the control group. The reliability of the microarray results was demonstrated by quantitative real-time polymerase chain reaction (qRT-PCR). Results. Of 235 differentially expressed genes, 150 were upregulated, while the other 85 were downregulated. Five miRNAs matched to every differential expression of circRNAs, and related MREs were predicted. We performed gene ontology (GO) analysis to identify the functions of their targeted genes, with the terms “Homophilic cell adhesion via plasma membrane adhesion molecules” and “Positive regulation of cellular process” showing the highest fold enrichment. Conclusions. This study demonstrated the role of circRNA expression profiling in the formation of IA and revealed that the mTOR pathway can be a latent therapeutic strategy for IA.

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