High Expression Of Circ Research Articles

Circ_PABPC1 promotes the malignancy of gastric cancer through interacting with ILK to activate NF-κB pathway

BackgroundGastric cancer (GC) is a common cancer type with both high incidence and mortality. Recent studies have revealed an important role of circRNA in the development of GC. However, more experiments are needed to reveal the precise molecular mechanisms of circRNA in GC development. MethodsBioinformatics analysis was conducted to predict the potential role of circ_PABPC1 in GC and the target proteins of circ_PABPC1. Quantitative RT-PCR, Western blot and immunohistochemistry assays were conducted to detect the levels of circ_PABPC1, NF-κB p65, NF-κB p65 (Ser536) and ILK. MTT, Edu staining, cell scratch-wound and trans-well assays were carried out to detect cell proliferation, migration and invasion. The interaction between ILK and circ_PABPC1 was confirmed by RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization assays. Genetically modified GC cells were injected into mice to evaluate the tumor growth performance. ResultsThis study found that the high expression of circ_PABPC1 was associated with a poor prognosis of GC. The up-regulation of circ_PABPC1 promoted the proliferation, migration and invasion of GC cells. Circ_PABPC1 bound to ILK protein, thereby preventing the degradation of ILK. ILK mediated the effect of circ_PABPC1 on GC cells through activating NF-κB. Conclusioncirc_PABPC1 promotes the malignancy of GC cells through binding to ILK to activate NF-κB signaling pathway.

Circ_MAPK9 promotes STAT3 and LDHA expression by silencing miR-642b-3p and affects the progression of hepatocellular carcinoma

BackgroundAberrant expression and activation of circular RNAs (circRNAs) are closely associated with various cancers. The role of circ_MAPK9 (hsa_circ_0001566) in cancer progression remains unknown. This study aims to investigate the function, mechanism and clinical significance of circ_MAPK9 in hepatocellular carcinoma (HCC).MethodsCirc_MAPK9 expression on the microarray of tumor from clinical HCC patients was detected by in situ hybridization (ISH). Circ_MAPK9 knockdown was achieved with siRNAs in SMMC-7721 and SK-Hep1 HCC cell lines. The biological function of circ_MAPK9 was verified in vitro by CCK8 test, colony formation assay, transwell assay, PI-Annexin V staining, and in vivo by xenograft tumor in nude mice. Fluorescent in situ hybridization (FISH), subcellular fractionation assay, a dual-luciferase reporter assay and rescue experiments were employed for further mechanistic investigation.ResultsThe expression of circ_MAPK9 was significantly up-regulated in HCC tissues and cells, which was found to be associated with poor prognosis. Patients with high expression of circ_MAPK9 had a shorter overall survival and disease-free survival in comparison to those with low circ_MAPK9 expression. Functional assays showed that circ_MAPK9 knockdown suppressed cellular proliferation, migration, invasion and tumor growth in vivo, and promoted apoptosis in HCC cells. Moreover, we found that circ_MAPK9 knockdown could inhibit aerobic glycolysis by decreasing the production of adenosine triphosphate (ATP) and lactic acid, which was mediated by lactate dehydrogenase (LDHA). Mechanistically, circ_MAPK9 functioned as ceRNA via sponging miR-642b-3p and alleviated the inhibitory effect of miR-642b-3p on its target signal transducer and activator of transcription 3 (STAT3) and LDHA, thereby leading to STAT3 activation and LDHA expression.ConclusionsCirc_MAPK9, as an oncogene, promotes HCC growth and metastasis through miR-642b-3p/STAT3-LDHA axis. Circ_MAPK9 could serve as a potential biomarker for HCC poor prognosis and diagnosis.

Circ_SIRT1 upregulates ATG12 to facilitate Imatinib resistance in CML through interacting with EIF4A3

Imatinib is the current gold standard for patients with chronic myeloid leukemia (CML). However, the primary and acquired drug resistance seriously limits the efficacy. To identify novel therapeutic target in Imatinib-resistant CML is of crucial clinical significance. CircRNAs have been demonstrated the essential regulatory roles in the progression and drug resistance of cancers. In this study, we identified a novel circRNA (circ_SIRT1), derived from the SIRT1, which is up-regulated in CML. The high expression of circ_SIRT1 is correlated with drug resistance in CML. Knockdown of circ_SIRT1 regulated K562/R cells viability, invasion and apoptosis. Besides, the inhibition of circ_SIRT1 attenuated autophagy level and reduced IC50 to Imatinib of K562/R cells. Mechanistically, circ_SIRT1 directly binds to the transcription factor Eukaryotic Translation Initiation Factor 4A3(EIF4A3) and regulated EIF4A3-mediated transcription of Autophagy Related 12 (ATG12), thereby affecting Imatinib resistance and autophagy level. Overexpression of ATG12 reversed the regulative effects induced by knockdown of circ_SIRT1. Taken together, our findings revealed circ_SIRT1 acted as a potential tumor regulator in CML and unveiled the underlying mechanism on regulating Imatinib resistance. circ_SIRT1 may serve as a novel therapeutic target and provide crucial clinical implications for Imatinib-resistant CML treatment.

Gene expression profiles of mRNA, lncRNA, miRNA, and circRNA and their clinical implications in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with complex pathophysiology and therapeutic strategies. Moreover, the molecular mechanisms underlying the pathogenesis of CRSwNP are incompletely understood. This study aimed to investigate the transcriptomic characteristics, ceRNA networks, and whether these molecular markers play a role in the occurrence and development of CRSwNP. Following RNA sequencing, a ceRNA network was predicted and constructed based on the sequencing results and multiple databases. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease ontology (DO) were applied to analyze the potential mechanisms in relation to the pathogenesis of CRSwNP. CIBERSORT was used to evaluate the immune cell infiltration levels in CRSwNP. The candidate genes of differentially expressed (DE) mRNA, DE-lncRNA, DE-miRNA, and DE-circRNA were verified by RT-qPCR, and the back-splice junction of circRNA was verified using Sanger sequencing. The clinical significance of differentially expressed genes was analyzed with correlation test and receiver operating characteristic curve. We identified 716 DE-mRNA, 230 DE-lncRNA, 42 DE-miRNA, and 46 DE-circRNA, and GO and KEGG enrichment analyses indicated that they were involved in multiple biological pathways, predominantly those associated with immunity and inflammation. DO analysis revealed CRSwNP is associated with diseases such as gastroesophageal reflux and allergic reactions. High expression of circ_0021727 was significantly and positively correlated with several important clinical indicators, and the area under the curve was 0.741. This study provides transcriptomic characteristics, which are potential biomarkers or therapeutic targets for the diagnosis and treatment of CRSwNP.

Circular RNA hsa_circ_0005218 promotes the early recurrence of hepatocellular carcinoma by targeting the miR-31-5p/CDK1 pathway

Increasing evidence has manifested that circular RNAs (circRNAs) exhibited critical function in regulating various signaling pathways related to hepatocellular carcinoma (HCC) recurrence. However, the role and mechanism of the circRNAs in the HCC early recurrence remain elusive. In this study, high-throughput RNA-sequencing (RNA-seq) analysis was conducted to identify the expression profile of circRNAs in HCC tissues and circ_0005218 was identified as one circRNA that significantly up-regulated in early recurrent HCC tissues. And patients with high expression of circ_0005218 showed worsen overall survival (OS) and disease-free survival (DFS). Moreover, the promotion effects of circ_0005218 on HCC cells in term of proliferation, invasion and metastasis were confirmed both in vitro and vivo by gain- and loss-of function assays. In addition, dual-luciferase reporter assays showed that circ_0005218 could competitively bind to micro-RNA (miR)-31-5p. Furthermore, we showed that suppression of CDK1 by miR-31-5p could be partially rescued by up-regulating circ_0005218. Taken together, the present study indicates that circ_0005218 absorbed miR-31-5p as a sponge to weaken its suppression on CDK1 expression, and thus boost HCC cell invasion and migration, which would act as a potential biomarker to predict the HCC early recurrence and as a new therapeutic target for treatment of HCC.

Predicting the influence of Circ_0059706 expression on prognosis in patients with acute myeloid leukemia using classical statistics and machine learning.

Background: Various circular RNA (circRNA) molecules are abnormally expressed in acute myeloid leukemia (AML), and associated with disease occurrence and development, as well as patient prognosis. The roles of circ_0059706, a circRNA derived from ID1, in AML remain largely unclear. Results: Here, we reported circ_0059706 expression in de novo AML and its association with prognosis. We found that circ_0059706 expression was significantly lower in AML patients than in controls (p < 0.001). Survival analysis of patients with AML divided into two groups according to high and low circ_0059706 expression showed that overall survival (OS) of patients with high circ_0059706 expression was significantly longer than that of those with low expression (p < 0.05). Further, female patients with AML and those aged >60years old in the high circ_0059706 expression group had longer OS than male patients and those younger than 60years. Multiple regression analysis showed that circ_0059706 was an independent factor-affecting prognosis of all patients with AML. To evaluate the prospects for application of circ_0059706 in machine learning predictions, we developed seven types of algorithm. The gradient boosting (GB) model exhibited higher performance in prediction of 1-year prognosis and 3-year prognosis, with AUROC 0.796 and 0.847. We analyzed the importance of variables and found that circ_0059706 expression level was the first important variables among all 26 factors included in the GB algorithm, suggesting the importance of circ_0059706 in prediction model. Further, overexpression of circ_0059706 inhibited cell growth and increased apoptosis of leukemia cells in vitro. Conclusion: These results provide evidence that high expression of circ_0059706 is propitious for patient prognosis and suggest circ_0059706 as a potential new biomarker for diagnosis and prognosis evaluation in AML, with high predictive value and good prospects for application in machine learning algorithms.

High Expression of circ_0001821 Promoted Colorectal Cancer Progression Through miR-600/ISOC1 Axis

It has been reported that circRNAs play an important regulatory role in the progression of colorectal cancer (CRC). However, the molecular role of circ_0001821 in CRC development is unclear. In this study, we aimed to investigate the regulatory role and molecular mechanisms of circ_0001821 in CRC. Reverse transcription-quantitative PCR and western blot assays were used to detect the expression of circ_0001821, miR-600 and isochorismatase domain containing 1 (ISOC1) in CRC tissues as well as its cell lines. Colony formation assay and EDU assay were used to detect the proliferative capacity of cells. Transwell assay was used to assess cell migration and invasion ability. Flow cytometry was used to analyze cell apoptosis. ELISA was used to measure the glycolytic capacity of cells. Dual-luciferase reporter assay and RNA pull-down assay were used to analyze the relationships between circ_0001821, miR-600 and ISOC1. Animal experimentation was used to validate the functional study of circ_0001821 in vivo. Immunohistochemistry (IHC) of Ki67 staining analysis was conducted to assess tumor growth. Circ_0001821 and ISOC1 were significantly increased in CRC tissues and its cell lines, and miR-600 was significantly decreased in CRC tissues and its cell lines. Silencing circ_0001821 inhibited cell proliferation, migration, invasion and glycolytic capacity, while inducing apoptosis. And it could inhibit tumor growth in vivo. Circ_0001821 could act as a sponge for miR-600 to regulate CRC processes. ISOC1 was identified as a downstream regulator of miR-600, also miR-600 could regulate the expression of ISOC1. In addition, circ_0001821 could regulate ISOC1 expression changes through miR-600. Mechanistically, either miR-600 inhibitor or overexpression of ISOC1 could reverse the effects of knockdown of circ_0001821 on cell biological properties. Circ_0001821 regulated the developmental process of CRC through miR-600/ISOC1 axis.

Circ_0000045 promotes proliferation, migration, and invasion of head and neck squamous cell carcinomas via regulating HSP70 and MAPK pathway

ObjectiveHead and neck squamous cell carcinoma (HNSCC) is one severe malignancy driven by complex cellular and signaling mechanisms. However, the roles of circular RNAs (circRNAs) in HNSCC’s development remains poorly understood. Therefore, this study investigated the functions of differentially expressed circRNAs in regulating HNSCC cell functions.MethodsDifferentially expressed circRNAs were characterized through RNA sequencing in HNSCC tissues. CircRNA’s identity was then confirmed using RT-PCR and Sanger’s sequencing. Next, expression levels of circRNA and mRNA were detected by qRT-PCR, after which protein abundances were measured by Western blotting. Subsequently, the proliferation, migration, and invasion of HNSCC cells was assessed by MTS, wound healing, and Transwell system, respectively, followed by identification of circRNA-binding proteins in HNSCC cells by circRNA pull-down, coupled with mass spectrometry.ResultsGreat alterations in circRNA profiles were detected in HNSCC tissues, including the elevated expression of circ_0000045. As observed, silencing of circ_0000045 effectively repressed the proliferation, migration, and invasion of HNSCC cell lines (FaDu and SCC-9). Contrarily, circ_0000045’s overexpression promoted the proliferation, migration, and invasion in FaDu and SCC-9 cells. Results also showed that circ_0000045 was associated with multiple RNA-binding proteins in HNSCC cells, such as HSP70. Moreover, circ_0000045 knockdown enhanced HSP70 expression and inhibited JNK2 and P38’s expression in HNSCC cells, which were oppositely regulated by circ_0000045’s overexpression.ConclusionThe high expression of circ_0000045; therefore, promoted cell proliferation, migration, and invasion during HNSCC’s development through regulating HSP70 protein and mitogen-activated protein kinase signaling.

Circ_0000291 contributes to hepatocellular carcinoma tumorigenesis by binding to miR-1322 to up-regulate UBE2T

Introduction and objectivesCircular RNAs (circRNAs) are identified to show important regulatory functions in cancer biology. We attempted to analyze the role of circ_0000291 in hepatocellular carcinoma (HCC) progression and its related mechanism. MethodsThe circular characteristic of circ_0000291 was tested using exonuclease RNase R. Cell proliferation was analyzed by 5-Ethynyl-2’-deoxyuridine (EdU) incorporation and colony formation assays. Cell apoptosis was measured by flow cytometry and a caspase 3 activity assay kit. Transwell assays were performed to analyze cell migration and invasion abilities. Sphere formation assay was conducted to analyze cell stemness. Dual-luciferase reporter and RNA-pull down assays were conducted to verify the interaction between microRNA-1322 (miR-1322) and circ_0000291 or ubiquitin conjugating enzyme E2 T (UBE2T). ResultsCirc_0000291 was markedly up-regulated in HCC tissues and cell lines. HCC patients with high expression of circ_0000291 displayed a low survival rate. Circ_0000291 knockdown restrained the proliferation, migration, invasion, and stemness and induced the apoptosis of HCC cells. Circ_0000291 directly interacted with miR-1322 and negatively regulated miR-1322 expression. Circ_0000291 knockdown-mediated anti-tumor impacts in HCC cells were largely overturned by the interference of miR-1322. miR-1322 directly paired with the 3’ untranslated region (3’UTR) of UBE2T, and UBE2T was negatively regulated by miR-1322. UBE2T overexpression largely reversed circ_0000291 silencing-induced effects in HCC cells. Circ_0000291 positively regulated UBE2T expression by absorbing miR-1322 in HCC cells. Circ_0000291 silencing notably reduced the tumorigenic potential in vivo. ConclusionCirc_0000291 facilitated HCC progression by targeting miR-1322/UBE2T axis, which provided novel potential biomarkers and targets for HCC patients.

Circular RNA_0001187 participates in the regulation of ulcerative colitis development via upregulating myeloid differentiation factor 88

ABSTRACT Circular RNA (circRNA) had been confirmed to participate in ulcerative colitis (UC) development. Circular RNA_0001187 (Circ_0001187) had been found to be overexpressed in patients with Crohn disease. Therefore, circ_0001187 might be an important circRNA regulating intestinal inflammatory diseases. However, the role and mechanism of circ_0001187 in UC progression remains unclear. The colonic mucosal tissues were obtained from 23 UC patients and 23 healthy normal controls. Tumor necrosis factor-α (TNF-α) was used to mimic UC cell model in vitro. Cell function was assessed by cell counting kit 8 assay, EdU assay, flow cytometry, ELISA assay and oxidative stress detection. RNA interaction was confirmed by dual-luciferase reporter assay and RIP assay. Serum exosomes were isolated by ultracentrifugation and identified by transmission electron microscope. Circ_0001187 was overexpressed in UC patients. Circ_0001187 knockdown enhanced the proliferation, while suppressed apoptosis, inflammation and oxidative stress of TNF-α-induced FHC cells. Circ_0001187 acted as miR-1236-3p sponge, and the effects of circ_0001187 downregulation on TNF-α-induced FHC cell injury were overturned by miR-1236-3p inhibitor. MYD88 was targeted by miR-1236-3p, and circ_0001187 sponged miR-1236-3p to regulate MYD88. MYD88 knockdown alleviated TNF-α-induced FHC cell injury, and its upregulation revoked the inhibition effect of miR-1236-3p on TNF-α-induced FHC cell injury. High expression of circ_0001187 also was observed in the serum exosomes of UC patients. Our data confirmed that circ_0001187 facilitated UC progression through miR-1236-3p/MYD88 axis, which might be a potential treatment and diagnosis biomarker for UC.

Circ_0004140 promotes LUAD tumor progression and immune resistance through circ_0004140/miR-1184/CCL22 axis

Lung adenocarcinoma (LUAD) is a highly prevalent cancer with high mortality. Immune resistance and tumor metastasis are the pivotal factors for the promotion of LUAD. CircRNAs have been revealed a crucial pre-clinical diagnostic and therapeutic potentials in LUAD. Herein, we identify a novel circRNA (circ_0004140), derived from the oncogene YAP1, which is up-regulated in LUAD. The high expression of circ_0004140 is correlated with poor prognosis and CTL cells dysfunction in LUAD patients. Knockdown of circ_0004140 regulated LUAD cells proliferation, migration, and apoptosis. Mechanistically, circ_0004140 served as a sponge of miR-1184 targeting C-C motif chemokine ligand 22(CCL22). Overexpression of CCL22 reversed the inhibitory effect induced by si-circ_0004140 on cells proliferation and migration. Moreover, we also revealed that elevated circ_ooo4140 was related to cytotoxic lymphocyte exhaustion, and a combination therapy of C-021 (CCL22/CCR4 axis inhibitor) and anti-PD-1 attenuated LUAD promotion and immune resistance. In conclusion, circ_0004140 may drive resistance to anti-PD-1 immunotherapy, providing a novel potential therapeutic target for LUAD treatment.

Circ_0001174 facilitates osteosarcoma cell proliferation, migration, and invasion by targeting the miR-186-5p/MACC1 axis

BackgroundStudies of aberrantly expressed circular RNAs (circRNAs) can provide insights into the molecular mechanisms of osteosarcoma (OS). However, the role of circ_0001174 in OS progression remains unknown. This study is aimed to identify differentially expressed circRNAs and messenger RNAs (mRNAs) in patients with OS and to investigate potential regulatory ways of circ_0001174.MethodsHigh-throughput sequencing was performed to screen aberrantly expressed circRNAs and mRNAs between tumor and paracancerous tissues from patients with OS. Several bioinformatics tools were used to analyze the functions and pathways of the differentially expressed genes between the tissues. Cell counting kit-8, cell migration and invasion assays were performed to evaluate the functions of the critical circRNAs. RNA interference experiments, quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to explore the relationship between miR-186-5p and circ_0001174 or metastasis-associated in colon cancer 1 (MACC1).ResultsCompared with the paracancerous tissues, 109 circRNAs and 1264 mRNAs were differentially expressed in the OS tissues, including 88 circRNAs and 707 mRNAs that were upregulated and 21 circRNAs and 557 mRNAs that were downregulated. The expression of four upregulated and four downregulated circRNAs was validated using RT-qPCR; the results were consistent with the sequencing data, and circ_0001174 was found to be significantly upregulated in 16 pairs of OS tissues and OS cell lines (fold change > 2.0, P value < 0.05). Knockdown of circ_0001174 inhibited the proliferation, migration, and invasion of OS cells. Additionally, circ_0001174 directly and negatively modulated the expression of miR-186-5p and positively regulated the expression of MACC1.ConclusionsAbnormally high expression of circ_0001174 may promote the proliferation, migration, and invasion of OS cells through up-regulating MACC1 by sponging miR-186-5p. These results provide insight into therapeutic targets for preventing and treating OS.

Circ_0092367 Inhibits EMT and Gemcitabine Resistance in Pancreatic Cancer via Regulating the miR-1206/ESRP1 Axis.

Gemcitabine is the first-line treatment for patients with pancreatic cancer (PC), yet most patients develop resistance to gemcitabine. Recent studies showed that circular RNAs (circRNAs) have important regulatory roles in PC progression and chemoresistance. In this study, the ability of circRNA circ_0092367 to enhance gemcitabine efficacy was tested and the underlying molecular mechanism of circ_0092367 was investigated. The expression levels of circ_0092367, miR-1206, and ESRP1 were measured using qRT-PCR experiments. The effects of circ_0092367, miR-1206, and ESRP1 on PC cell lines exposed to gemcitabine were examined by CCK-8 assays. We performed luciferase assays to determine the relationship between circ_0092367 and miR-1206 and between miR-1206 and ESRP1. We demonstrated that circ_0092367 was significantly downregulated in PC tissues and cell lines, and a high expression of circ_0092367 was associated with improved survival in patients with PC. Gain- and loss-of-function assays revealed that circ_0092367 inhibited epithelial–mesenchymal transition (EMT) phenotypes and sensitized PC cells to gemcitabine treatment in vitro and in vivo. Cytoplasmic circ_0092367 could directly repress the levels of miR-1206 and thus upregulate the expression of ESRP1, thereby inhibiting EMT and enhancing the sensitivity of PC cells to gemcitabine treatment. Our findings show that circ_0092367 plays a crucial role in sensitizing PC cells to gemcitabine by modulating the miR-1206/ESRP1 axis, highlighting its potential as a valuable therapeutic target in PC patients.

Hsa_circ_0011385 knockdown represses cell proliferation in hepatocellular carcinoma

Circular RNAs (circRNAs), continuous loops of single-stranded RNA, regulate gene expression during the development of various cancers. However, the function of circRNAs in hepatocellular carcinoma (HCC) is rarely discussed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA levels of circ_0011385, miR-361-3p, and STC2 in 96 pairs of HCC tissues (tumor tissues and adjacent normal tissues), HCC cell lines, and L02 (human normal liver cell line) cells. The relationships between circ_0011385 expression and clinical features of HCC were evaluated. Functional experiments in vitro or in vivo were used to evaluate the biological function of circ_0011385. Bioinformatics analysis was performed to predict miRNAs and mRNAs sponged by circ_0011385. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays were used to elucidate the interactions among circ_0011385, miR-361-3p, and STC2 (stanniocalcin 2). ChIP and dual-luciferase reporter gene assays were used to identify the upstream regulator of circ_0011385. High expression of circ_0011385 was observed in HCC tissues and cell lines and was significantly associated with tumor size, TNM stage, and prognosis. In addition, inhibition of circ_0011385 expression prevented the proliferation of HCC cells in vitro and in vivo. Circ_0011385 sponged miR-361-3p, thereby regulating the mRNA expression of STC2. In addition, the transcription of circ_0011385 was regulated by SP3. Circ_0011385 knockdown suppressed cell proliferation and tumor activity in HCC. Circ_0011385 may therefore serve as a new biomarker in the diagnosis and treatment of HCC.

Circular RNA 0014715 Facilitates Cell Proliferation and Inhibits Apoptosis in Esophageal Squamous Cell Carcinoma.

BackgroundCircular RNAs (circRNAs) have recently been verified to have multiple biological functions and participate in diverse biological processes in different malignant tumors, including esophageal squamous cell carcinoma (ESCC). Nonetheless, the function of circular RNA 0014715 (hsa_circ_0014715, circ_0014715) in ESCC has not been described.Materials and MethodsWe investigated clinical data from sixty-seven patients undergoing surgery for esophageal cancer. The clinical data were collected. And we analyzed the correlation between the clinical characteristics of these patients and the expression of circ_0014715. Besides, we explored the expression of circ_0014715 in ESCC cell lines. We used cell counting kit-8, colony formation, transwell assay, and flow cytometry to detect changes in cell proliferation, migration, apoptosis, and cell cycle progression.ResultsWe found that circ_0014715 was highly expressed in esophageal squamous cell carcinoma tissues and cell lines. The correlation analysis of clinicopathological features and gene expression revealed that high expression of circ_0014715 was related to nerve invasion, vascular invasion, more advanced tumor-node-metastasis (TNM) stage and poor differentiation grade. Receiver operating characteristic (ROC) curves revealed that circ_0014715 might have diagnostic value for ESCC. Experiments with cultured cells showed that knockdown of circ_0014715 significantly restrained cell proliferation, migration, invasion, wound healing and accelerated cell apoptosis. And cell cycle arrest at G2 phase was observed via flow cytometry. Overexpression of circ_0014715 caused the opposite effects. Collectively, these studies show that circ_0014715 is closely connected with the pathogenesis and development of ESCC. The excess expression of circ_0014715 may have promoting effects on the progression of esophageal cell carcinoma.ConclusionOur finding revealed that circ_0014715 promoted tumor growth and cell proliferation. All of these suggest that targeting circ_0014715 has potential therapeutic value in the treatment of ESCC.

Circ_0001944 Contributes to Glycolysis and Tumor Growth by Upregulating NFAT5 Through Acting as a Decoy for miR-142-5p in Non-Small Cell Lung Cancer.

BackgroundCircular RNAs (circRNAs) participate in the tumorigenesis of various cancers. CircRNA hsa_circ_0001944 (circ_0001944), derived from the TCONS_l2_00030860 gene, has been uncovered to be upregulated in NSCLC (non-small cell lung cancer). Nevertheless, the influence of circ_0001944 on glycolysis and tumor growth in NSCLC is unclear.MethodsExpression trend of circ_0001944 in NSCLC tissues and cells were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to assess the influence of circ_0001944 knockdown on proliferation, migration, invasion, and glycolysis of NSCLC cells. Protein levels were assessed by Western blotting. The regulatory mechanism of circ_0001944 was analyzed by bioinformatics analysis, dual-luciferase reporter assay, and/or RNA pull-down assay. The tumorigenicity of circ_0001944 was confirmed by xenograft assay.ResultsCirc_0001944 was highly expressed in NSCLC, and NSCLC patients with high expression of circ_0001944 had a worse prognosis. Circ_0001944 silencing decreased xenograft tumor growth in vivo and repressed proliferation, migration, invasion, and glycolysis of NSCLC cells in vitro. Circ_0001944 was verified as a decoy for microRNA (miR)-142-5p, which targeted NFAT5 (nuclear factor of activated T cells 5). MiR-142-5p was downregulated while NFAT5 was upregulated in NSCLC. Both miR-142-5p inhibition and NFAT5 overexpression offset the suppressive impact of circ_0001944 silencing on proliferation, migration, invasion, and glycolysis of NSCLC cells. Circ_0001944 adsorbed miR-142-5p to elevate NFAT5 expression in NSCLC cells.ConclusionCirc_0001944 promotes proliferation, migration, invasion, and glycolysis of NSCLC cells by upregulating NFAT5 through adsorbing miR-142-5p, offering a novel mechanism for understanding the advancement of NSCLC.

Circ_0023028 contributes to the progression of laryngeal squamous cell carcinoma by upregulating LASP1 through miR-486-3p.

Circular RNAs (circRNAs) are implicated in the tumorigenesis of human cancers. However, the effects of circRNAs on laryngeal squamous cell carcinoma (LSCC) are largely unknown. Here, we aimed to explore the roles of circ_0023028 in LSCC development. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure circ_0023028, miR-486-3p, and Lin-Isl-Mec (LIM) and SH3 domain protein 1 (LASP1) mRNA. The characteristics of circ_0023028 were determined by RNase R digestion assay and Actinomycin D assay. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized for cell proliferation. Transwell assay was adopted for cell invasion and migration. Flow cytometry analysis was carried out to analyze cell cycle and apoptosis. RNA pull-down assay and dual-luciferase reporter assay were used to explore the association between miR-486-3p and circ_0023028 or LASP1. Western blot assay was adopted to measure LASP1 protein level. Murine xenograft model was executed to investigate the function of circ_0023028 in vivo. High expression of circ_0023028 was observed in LSCC tissues and cells. Circ_0023028 was stable and possessed a loop structure. Circ_0023028 silencing suppressed LSCC cell proliferation, metastasis and cell cycle process and induced apoptosis in vitro and hampered tumor growth in vivo. Further mechanism analysis demonstrated that circ_0023028 could sponge miR-486-3p to regulate LASP1 expression in LSCC cells. The malignant behaviors of LSCC cells mediated by circ_0023028 knockdown were rescued by the inhibition of miR-486-3p. Moreover, miR-486-3p suppressed LSCC cell progression via binding to LASP1. Circ_0023028 knockdown might impede the progression of LSCC by regulating miR-486-3p/LASP1 axis, which could provide a novel insight on the mechanism of LSCC progression.

Circular RNA 0081146 facilitates the progression of gastric cancer by sponging miR-144 and up-regulating HMGB1.

Recent studies have revealed that circular RNA (circRNA) plays a pivotal role in cancer development. The study aimed to investigate the role of circ_0081146 in gastric cancer (GC). Circ_0081146 was upregulated in GC tissues and cells. Patients with high expression of circ_0081146 had a significantly reduced 5-year overall survival rate. Circ_0081146 knockdown restrained the growth, migration and invasion of GC cells in vitro as well as tumorigenesis in vivo. Circ_0081146 targeted miR-144 and HMGB1 was targeted by miR-144. Circ_0081146 was negatively correlated with miR-144 expression, while positively correlated with HMGB1 expression in GC tissues. Moreover, the inhibitory effect of circ_0081146 knockdown on the progression of GC cells were reversed by silencing miR-144 or HMGB1 overexpression. Mechanically, circ_0081146 increased HMGB1 expression by targeting miR-144. Circ_0081146 functions as an oncogene in GC to promote cell growth, migration and invasion via modulating the miR-144/HMGB1 axis.

Circular RNA circ_0062389 modulates papillary thyroid carcinoma progression via the miR-1179/high mobility group box 1 axis

ABSTRACT Circular RNAs (circRNAs) feature prominently in regulating the progression of tumors, including papillary thyroid carcinoma (PTC). This work is designated to delve into the role of circ_0062389 in PTC. Generally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect circ_0062389, miR-1179 and high mobility group box 1 (HMGB1) mRNA expression levels. RNase R assay was used to verify the circular characteristics of circ_0062389. After circ_0062389 was knocked down in PTC cells, CCK-8 assay was adopted to determine cell viability. Wound healing assay was leveraged to probe cell migration. Besides, Western blot assay was executed to examine the expression levels of HMGB1 and epithelial-mesenchymal transformation (EMT)-related markers (E-cadherin and N-cadherin). Dual-luciferase reporter assay was performed to authenticate the targeting relationships between miR-1179 and circ_0062389, as well as miR-1179 and HMGB1. Here, this work proved that circ_0062389 was greatly up-regulated in PTC tissues and cell lines. The high expression of circ_0062389 was related to large tumor size and positive lymphatic metastasis. Knocking down circ_0062389 could inhibit the proliferation, migration and EMT process of PTC cells. Besides, miR-1179 was a downstream molecule of circ_0062389. Furthermore, miR-1179 inhibitors could partially reverse the above effect of knocking down circ_0062389 on PTC cells. It was also confirmed that HMGB1 was a direct target of miR-1179 and mediated the effects of circ_0062389 and miR-1179 in PTC. Altogether, circ_0062389 can adsorb miR-1179, and regulate HMGB1 expression, thus playing a role in PTC.

CircRNA circ_0001821 predicts an unfavorable prognosis and promotes the proliferation of multiple myeloma

ABSTRACT Background A previous study reported circ_0001821 serves as a new diagnostic biomarker in lung and gastric cancer. However, whether circ_0001821 associates with the development of multiple myeloma is still unclear. Objective To investigate the clinical significance and biological function of circ_0001821 in human multiple myeloma. Methods The expression of circ_0001821 in bone marrow tissues and cell lines of multiple myeloma was detected by quantitative real-time PCR. The relationship between circ_0001821 expression and clinicopathological characteristics in multiple myeloma patients was determined by the Chi-square test. MTT, Western blotting analysis and flow cytometry were performed to evaluate the impact of circ_0001821 on cell proliferation and apoptosis. Results Circ_0001821 expression was increased in bone marrow tissues and cell lines from multiple myeloma compared with that in normal controls, and its expression was related to hemoglobin, bone injury, β2-MG, and globulin. In multiple myeloma patients aged ≥60 years, high circ_0001821 expression displayed lower overall survival (OS) rate compared with low circ_0001821 expression. High circ_0001821 expression was an independent prognostic indicator for the poor OS. Furthermore, the expression of Caspase-3 protein was lower in patients with high circ_0001821 expression than that in those patients with low circ_0001821expression. Overexpression of circ_0001821 led to increased proliferation and arrested apoptosis of multiple myeloma cells, while knockdown of circ_0001821 had the opposite effects. Conclusion High expression of circ_0001821 associated with aggressive pathological indicators and predicted a poor prognosis in multiple myeloma. Circ_0001821 played an oncogenic role in multiple myeloma by modulating cell proliferation and apoptosis.