Down-regulation Of Circ Research Articles

WITHDRAWN: Circ_0001946 facilitates the proliferation and represses apoptosis of ox-LDL-stimulated Vascular Smooth Muscle Cells via regulating miR-641/CCND1 pathway

Abstract Recently, circRNAs are reported to exhibit significant regulation on atherosclerosis development. Circ_0001946 has been identified in several diseases and our present study was aimed to investigate its biological roles on Vascular Smooth Muscle Cells (VSMCs) incubated with ox-LDL. In our research, we validated circ_0001946 was obviously increased in human atherosclerosis patient serums. ox-LDL induced circ_0001946 expression in VSMCs. Meanwhile, we reported miR-641 was obviously decreased in atherosclerosis serum samples compared to the health controls. It was indicated silence of circ_0001946 repressed VSMCs proliferation and contributed to the cell apoptosis. In addition, we observed that down-regulation of circ_0001946 induced miR-641 expression greatly and their direct correlation was proved using dual-luciferase reporter assay. Inhibitors of miR-641 rescued the effects of depletion of circ_0001946 on proliferation and apoptosis in VSMCs treated by ox-LDL. In addition, amplification and overexpression of cyclin D1 (CCND1), which can alter cell cycle progression, is dys-regulated in a variety of diseases. It was showed that CCND1 could be a target of miR-641 and circ_0001946 acted as a sponge of miR-641 to increase CCND1 level. In conclusion, our current data suggested circ_0001946 silence inhibited VSMCs proliferation and increased cell apoptosis through modulating miR-641 and CCND1.

Circular RNA circ_0000284 plays an oncogenic role in the progression of non-small cell lung cancer through the miR-377-3p-mediated PD-L1 promotion

BackgroundCircular RNAs (circRNAs), a subgroup of non-coding RNAs, are recognized as pivotal mediators in various types of cancers. CircRNA_0000284 (circ_0000284) was manifested to participate in the development of non-small cell lung cancer (NSCLC). The novel functional mechanism of circ_0000284 in NSCLC was investigated in our current study.MethodsWe exploited quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the relative RNA (circRNA, miRNA and mRNA) expression. The assessment of cell proliferation and colony formation was executed by Cell Counting Kit-8 (CCK-8) and colony formation assay, respectively. Transwell assay was implemented to examine cell migration and invasion. All protein levels were assayed using western blot. The role of circ_0000284 in vivo was evaluated via xenograft model. The target relation was estimated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.ResultsAs for the biological characterization, circ_0000284 was highly stable and localized in the cytoplasm. Circ_0000284 was up-regulated in NSCLC and could predict poor prognosis of NSCLC patients. Both in vitro and in vivo, down-regulation of circ_0000284 refrained tumorigenesis of NSCLC. Besides, microRNA-377-3p (miR-377-3p) was a miRNA target of circ_0000284, and targeted programmed death-ligand 1 (PD-L1). Circ_0000284 was a cancer-promoting circRNA in NSCLC via regulating the miR-377-3p/PD-L1 axis.ConclusionThus, our results unraveled that circ_0000284 facilitated the progression of NSCLC by up-regulating the PD-L1 expression as a competing endogenous RNA (ceRNA) of miR-377, possibly developing a different perspective in understanding the molecular pathogenesis of NSCLC.

Suppression of Circular RNA Hsa_circ_0109320 Attenuates Non-Small Cell Lung Cancer Progression via MiR-595/E2F7 Axis.

BackgroundCircular RNAs (circRNAs) are frequently aberrantly expressed in non-small cell lung cancer (NSCLC) and are considered to exert a pivotal role in the occurrence and development of NSCLC via targeting and negatively regulating microRNAs (miRNAs). We aimed to investigate the role of hsa_circ_0109320 in the proliferation, invasion and apoptosis of NSCLC, and explore its underlying molecular mechanism.Material/MethodsReverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to determine the circ_0109320 and miR-595 expression in tissues or cells. Western blot analysis was conducted to examine the cleaved caspase-3, Bax, Bcl-2, and E2F7 protein expression. Transwell detection was used to evaluate the invasion level of NSCLC cell lines.ResultsThe results of present study indicated that circ_0109320 expression in NSCLC patients was upregulated significantly in tumor tissues compared with tissues adjacent to carcinoma. Upregulated circ_0109320 level was significantly associated with TNM stages as well as lymph node metastasis of NSCLC. Moreover, downregulation of circ_0109320 attenuated proliferation and invasion while promoting apoptosis in NSCLC cells. We further confirmed that circ_0109320 could sponge miR-595 to upregulate E2F7 expression. Silencing of miR-595 or overexpression of E2F2 could partially reversed the inhibitory role of circ_0109320 knockdown in NSCLC cells. These data provided evidence that the suppression of circ_0109320 attenuates NSCLC cell proliferation and invasion and enhances apoptosis through the miR-595/E2F7 pathway.ConclusionsCirc_0109320/miR-595/E2F2 axis may exert a pivotal role in the pathological mechanism of NSCLC progression, and it has potential application in the future treatment of NSCLC.

Circular RNA-UBXN7 promotes proliferation, migration and suppresses apoptosis in hepatocellular cancer

Objective: To investigate the effect and molecular mechanism of circular RNA-UBXN7 (circ_UBXN7) on the proliferation, migration and apoptosis of hepatocellular carcinoma cells. Methods: Circ_UBXN7 expression in the tissues and cells of hepatocellular cancer was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and the relationship between circ_UBXN7 expression and clinicopathological features, including age, gender, tumor volume, pathological classification, staging, and lymph node metastasis was analyzed. The full-length sequence of circ_UBXN7 with lentivirus carrying lenti circ_UBXN7 and lenti circ_UBXN7 shRNA was constructed to transfect hepatocellular cell lines (HepG2 and Huh-7), respectively. CCK-8 experiments were performed to detect the ability of up- or down-regulation of circ_UBXN7 on the proliferation of HEPG2 and HUH-7 cells. Annexin V / PI experiment was used to detect the changes in apoptosis of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. JC-1 assay was used to detect the changes in mitochondrial potential energy of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. Transwell was used to detect the migration ability of HEPG2 and HUH-7 cells after up-regulation or down-regulation of circ_UBXN7 expression. Western blotting was used to detect the expressional change of TWIST, E-cadherin, N-cadherin and vimentin. Statistical analysis: The expression levels of circ_UBXN7 and clinicopathological features were measured by chi-square test. Two groups were compared by t-test and three groups and above were compared by single factor analysis of variance. LSD method was used for comparison between groups. Results: The expression of circ_UBXN7 in liver cancer tissues was significantly higher than adjacent tissues, and its expression level was significantly positively correlated with tumor volume, stage, and lymph node metastasis (P < 0.05). Lenti-circ_UBXN7 had up-regulated the expression of circ_UBXN7 in HEPG2 and HUH-7 cells and promoted cell proliferation. Lenti-circ_UBXN7-shRNA had down-regulated the expression of circ_UBXN7 and induced apoptosis. Lenti-circ_UBXN7-shRNA had reduced the mitochondrial membrane potential of cells. Lenti-circ_UBXN7 had promoted cell migration, while lenti-circ_UBXN7-shRNA had inhibited cell migration. Lenti-circ_UBXN7 had induced increased expression of Twist, N-cadherin, and Vimentin proteins, and reduced the expression of E-cadherin protein. Lenti-circ_UBXN7-shRNA had opposite effects on the expression levels of each protein. Starbase V2.0 software showed that miR-203a and circ_UBXN7 had potential binding sites, and miR-203a and circ_UBXN7 expression levels were negatively correlated in HEP ​​G2 and HUH-7 cells. Conclusion: circ_UBXN7 plays an important role in promoting the occurrence and development of liver cancer, and is expected to become a potential target for the treatment of liver cancer.

Circ_0067934 correlates with poor prognosis and promotes laryngeal squamous cell cancer progression by sponging miR-1324.

As a kind of non-coding RNA, circular RNA (circRNA) plays a regulatory role in many tumors. Our intention was to investigate the clinical significance, biological function, and molecular regulation mechanisms of circ_0067934 in laryngeal squamous cell cancer (LSCC) progression. The expression levels of circ_0067934 in LSCC tumor samples and cells were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The associations of circ_0067934 expression with clinicopathological features and overall survival in LSCC patients were statistically analyzed. The biological function of circ_0067934 in LSCC cells was analyzed by CCK-8, colony formation, EdU, and transwell assays. Dual-Luciferase reporter assay was conducted to verify that circ_0067934 may sponge miR-1324 to regulate proliferation and migration of LSCC. Circ_0067934 expression was remarkably upregulated in LSCC tissues and cells. High level of circ_0067934 was significantly related to tumor size, lymph node status, and distant metastasis of LSCC. Furthermore, highly expressed circ_0067934 could result in notably worse survival. In vitro experiments showed that down-regulation of circ_0067934 inhibited proliferation and migration of LSCC cells. Mechanism analysis revealed that circ_0067934 regulated LSCC development by sponging miR-1324. Circ_0067934 may function as an oncogene in LSCC, which provided a feasible prognostic biomarker and therapeutic target for LSCC.

Circular RNA hsa_Circ_101141 as a Competing Endogenous RNA Facilitates Tumorigenesis of Hepatocellular Carcinoma by Regulating miR-1297/ROCK1 Pathway

As a novel class of noncoding RNAs, circular RNAs (circRNAs) have been recently reported to be involved in cell development and function. However, the functional role of circRNAs in hepatocellular carcinoma (HCC) remains unclear. In the present study, we found that the expression of human circ_101141 was upregulated in HCC tissues and cells. In addition, downregulation of circ_101141 dramatically inhibited cell proliferation, migration, and invasion in HCC cells. In addition, by using the bioinformatics tools, the potential target of circ_101141 was predicted. Mechanistic investigations indicated that circ_101141 acted as a miR-1297 “sponge”; meanwhile, Rho-associated, coiled-coil-containing protein kinase 1 (ROCK1) was a direct target of miR-1297. Further experiments demonstrated that circ_101141 contributed to the progression of HCC by acting as competing endogenous RNA (ceRNA) of miR-1297 to regulate ROCK1 expression. Furthermore, knockdown of circ_101141 attenuated HCC tumorigenesis in vivo. Taken together, these findings indicated that circRNA circ_101141 acted as a ceRNA to facilitate tumorigenesis of HCC by regulating miR-1297/ROCK1 pathway.

Circ_0091579 promotes proliferative ability and metastasis of liver cancer cells by regulating microRNA-490-3p.

To explore the role of Circular RNA 0091579 in the progression of liver cancer (LCa) and its molecular mechanism. Quantitative polymerase chain reaction (qPCR) was used to detect circ_0091579 expression levels in LCa tissues and adjacent tissues, which was further verified in LCa cells and normal liver epithelial cells. After circ_0091579 was knocked down in Huh7 and HepG2 cells, cell counting kit-8 (CCK-8), plate cloning and transwell assays were performed to verify the effect of circ_0091579 on cell proliferative ability and metastasis of LCa cells. The starBase database was used to search for microRNAs that could interact with circ_0091579, and the Dual-Luciferase reporter gene was used to verify their binding relationship. circ_0091579 was highly expressed in HCC and HCC cells. In vitro experiments showed that down-regulation of circ_0091579 expression could remarkably inhibit the proliferative ability and metastasis of HCC cells. Bioinformatics software predicted the binding sites between circ_0091579 and microRNA-490-3p, and dual-luciferase reporter gene assay confirmed the binding relationship between circ_0091579 and microRNA-490-3p. qPCR results showed that microRNA-490-3p was remarkably down-regulated in LCa tissues. In vitro experiments confirmed that overexpression of microRNA-490-3p inhibited the proliferative ability and metastasis of HCC cells. circ_0091579 is abnormally highly expressed in LCa tissues and cells. Down-regulation of circ_0091579 can inhibit the proliferative ability and metastasis of HCC cells by regulating microRNA-490-3p, thus accelerating the progress of the tumor.

Circ_ANKIB1 stabilizes the regulation of miR-19b on SOCS3/STAT3 pathway to promote osteosarcoma cell growth and invasion.

Osteosarcoma is a highly malignant tumor. The molecular mechanism of its occurrence and development has not yet been clarified. Current studies have found that noncoding RNAs, such as circular RNAs (circRNAs) and microRNAs (miRNAs), play important regulatory roles in the progression of diseases. Our previous studies have shown that miR-19b is an oncogene in osteosarcoma. Further studies have shown that circ_ANKIB1 has binding sites for miR-19b, and both molecules were generally upregulated in osteosarcoma cells. RIP assay, RNA pull down, and dual-luciferase reporter gene assay showed that circ_ANKIB1 could directly bind to miR-19b and act as an miR-19b sponge in osteosarcoma cells. Circ_ANKIB1 promoted miR-19b expression, inhibited the expression of the downstream target gene SOCS3, and then activated the STAT3 pathway. When cotransfected with circ_ANKIB1 siRNA, and miR-19b mimics, the expression of SOCS3 and the phosphorylation level of STAT3 did not change significantly. Continuous detection of cell growth and invasion showed that the downregulation of circ_ANKIB1 or miR-19b significantly inhibited cell proliferation and invasion, but increased the apoptotic level. When cotransfected with circ_ANKIB1 siRNA and miR-19b mimics or SOCS3 siRNA, the cell proliferation, apoptosis, and invasion levels did not change significantly, suggesting that circ_ANKIB1 could affect the STAT3 pathway and osteosarcoma cell growth and invasion by enhancing the regulation of miR-19b on the downstream target gene SOCS3. These findings suggest that circRNAs stabilize miRNA functions, and further studies on this new function of circRNAs will provide a meaningful reference for the diagnosis and treatment of tumors and other diseases.

Down-Regulation of Circular RNA_000926 Attenuates Renal Cell Carcinoma Progression through miRNA-411–Dependent CDH2 Inhibition

Many studies have recognized that circular RNAs (circRNAs) can be promising targets for renal cell carcinoma (RCC) by acting as competing endogenous RNAs for miRNAs. This study intends to uncover the implication of a novel circRNA, circ_000926 in RCC, and how it affects tumorigenesis. Microarray-based circRNA/gene expression profiling of RCC was used to identify differentially expressed circRNAs/genes in RCC and normal tissues. miRNAs targeting the screened circRNAs/genes were predicted online, followed by analyzing circ_000926 expression in RCC. The crosstalk among circ_000926, miRNA-411 (miR-411), and CDH2 was then validated. The expression of circ_000926, miR-411, and cadherin 2 (CDH2) was up-regulated or down-regulated in RCC cells to unearth their effects on the biological behaviors of RCC cells. circ_000926 was highly expressed in RCC tissues and cell lines, whereas CDH2 was verified to be a target of miR-411. As a competing endogenous RNA, circ_000926 could directly bind to miR-411 to up-regulate CDH2. Down-regulation of circ_000926 resulted in inhibited growth, migration, and invasion abilities of RCC cells, as well as suppressed epithelial-mesenchymal transition and tumor growth. However, the inhibition of miR-411 or elevation of CDH2 reversed the antitumor effects induced by silencing circ_000926. Down-regulation of circ_000926 exerts an inhibitory effect on RCC progression through miR-411-dependent CDH2 inhibition, highlighting a potential target for RCC treatment.

Circ_0017247 accelerates epithelial-mesenchymal transition in non-small cell lung cancer.

Recently, the vital role of circular RNAs is discovered in many diseases, including tumor progression. Non-small cell lung cancer (NSCLC) is one of the most ordinary malignant tumors. The purpose of our study is to detect the potential function of circ_0017247 in NSCLC to offer new biomarkers and targets. The level of circ_0017247 in NSCLC tissues and cell lines was monitored by Rea Time-quantitative Polymerase Chain Reaction (RT-qPCR). Pearson's Chi-square test was used to determine the association between circ_0017247 expression and several clinicopathological factors. Then, circ_0017247 was knocked down in NSCLC cells to uncover its function in metastasis of NSCLC. Cell migrated and invaded ability was measured through transwell assay, Matrigel assay, and wound healing assay. The Western blot assay was performed to analyze the effect of circ_0017247 on the epithelial-mesenchymal transition (EMT) process. In the research, the expression level of circ_0017247 was significantly increased in NSCLC tissues compared with that in the adjacent samples. Circ_0017247 expression was associated with lymphatic metastasis. The expression of circ_0017247 was also increased in NSCLC cell lines. Downregulation of circ_0017247 led to the inhibition of cell migration and invasion in NSCLC. In addition, results of further experiments revealed that the EMT-related proteins were regulated via the knockdown of circ_0017247 in NSCLC. Circ_0017247 could enhance cell migration and invasion of NSCLC by inducing EMT process.

Downregulation of circ_0132266 in chronic lymphocytic leukemia promoted cell viability through miR-337-3p/PML axis.

Circular RNAs (circRNAs) have recently been reported to play crucial roles in various regulatory processes and involved in cancer onset and progression. However, the potential mechanism of circRNAs in chronic lymphocytic leukemia (CLL) remains largely unknown. Here, we observed hsa_circ_0132266 (circ_0132266), a circRNA significantly decreased in the peripheral blood mononuclear cells (PBMCs) of CLL patients compared with healthy donors, could act as an endogenous sponge of hsa-miR-337-3p (miR-337-3p) and regulate its activity, which resulted in a downstream change of target-gene PML and a consequent influence on cell viability. Taken together, our data indicated the regulatory mechanism of circ_0132266 in CLL progression through circ_0132266/miR-337-3p/PML axis, suggesting that it may serve as a biomarker as well as an exploitable therapeutic target for CLL.

Circ_0005075 promotes hepatocellular carcinoma progression by suppression of microRNA-335.

Accumulating evidence suggests that noncoding RNAs play a vital role in cancer biology. Circular RNAs (circRNAs), a newly defined class of endogenously widespread noncoding RNAs, have been intensively reported to influence cell function and development, and even cancer prognosis by sponging microRNAs in various types of cancer. Nevertheless, the circRNAs research in hepatocellular carcinoma (HCC) still remains far insufficient. Herein, we investigated the role of a newly defined circRNAs, circ_0005075, in HCC development. We found circ_0005075 was upregulated in HCC tissues. HCC progression was suppressed by downregulation of circ_0005075 in vitro and in vivo, and the suppression was partially reversed by inhibition of microRNA-335 (miR-335) expression. Further, we found the expression of mitogen-activated protein kinase 1 (MAPK1) was substantially regulated by circ_0005075 and miR-335. Mechanically, it was demonstrated that circ_0005075 could directly bind to miR-335 and miR-335 could bind to MAPK1. Our data provide evidence that circ_0005705 promotes the HCC progression by sponging miR-335 and further regulating MAPK1 expression.

Circular RNA circ_0026134 regulates non-small cell lung cancer cell proliferation and invasion via sponging miR-1256 and miR-1287

Non-small cell lung cancer (NSCLC) is the major type of lung malignancy with increasing incidence worldwide. Despite progression in diagnosis and management of NSCLC, the patients’ survival rate is still unfavorable. Accumulating data have shown that circular RNAs (circRNAs) act as key roles in oncogenesis. In this project, circ_0026134 expression in NSCLC tissue specimens and cells was measured by RT-qPCR. The functional roles (cell growth, apoptosis, migration, and invasion) of circ_0026134 were investigated by gain and loss-of-function assays. In addition, luciferase reporter assay was used to uncover the mechanisms of circ_0026134. Circ_0026134 was frequently upregulated in NSCLC samples and cell lines. Furthermore, we observed that downregulation of circ_0026134 attenuated NSCLC cell proliferation and metastatic properties and induced cell apoptosis. The overexpression of circ_0026134 in NSCLC cells caused the opposite effect. For the part of mechanism exploration, miR-1256 and miR-1287 were proved to be sponged by circ_0026134. Rescue experiments further indicated that the oncogenic role of circ_0026134 was dependent on its regulation of miR-1256 and miR-1287. Taken together, this study may provide a new insight and treatment target for NSCLC.

CircRNA has_circ_0006427 suppresses the progression of lung adenocarcinoma by regulating miR-6783–3p/DKK1 axis and inactivating Wnt/β-catenin signaling pathway

Recently, circular RNAs (circRNAs) are identified as a novel class of noncoding RNAs playing important roles in human malignant tumors. However, the regulatory function of circRNA in lung adenocarcinoma (LUAD) is still largely unknown. Present study aimed to explore the role of circ_0006427 in LUAD progression. Firstly, the downregulation of circ_0006427 in LUAD tissues and cell lines was revealed by microarray analysis and qRT-PCR analysis. And we also confirmed the circ_0006427 as a prognostic target in LUAD patients. Functionally, overexpression of circ_0006427 effectively suppressed cell proliferation, migration and invasion. Mechanistically, circ_0006427 was found to be predominantly located in the cytoplasm of LUCA cell, and was further revealed to positively regulate DKK1 in LUAD by sponging miR-6783–3p. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and western blot analysis revealed that circ_0006427 inactivated Wnt/β-catenin signaling pathway by upregulating DKK1. At last, rescue assays proved the function of circ_0006427/miR-6783–3p/DKK1 axis in LUAD progression. In conclusion, our study revealed that circ_0006427 suppressed lung adenocarcinoma progression through regulating miR-6783–3p/DKK1 axis.

Circ_0058063 regulates CDK6 to promote bladder cancer progression by sponging miR-145-5p.

The study was aimed to investigate the influence of circ_0058063 on tumorigenesis as well as the regulatory mechanism of circ_0058063/miR-145-5p/ CDK6 pathway in bladder cancer (BC). Bioinformatics analysis was used to screen highly expressed circle RNA (circRNA) and search its downstream microRNA (miRNA) and protein. The expression level of circRNA, miRNA, and CDK6 in BC cell lines T24 and J82 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Small interfering RNA was used to downregulate circ_0058063 expression. Cell proliferation, cell cycle, cell apoptosis, and cell migration of T24 cells and J82 cells were detected through MTT assay, flow cytometry, and wound-healing assay, respectively. The relationships among miR-145-5p, circ_0058063, and CDK6 were confirmed through dual luciferase reporter assay. In vivo experiment was also performed to explore the impact of circ_0058063/miR-145-5p/ CDK6 pathway on tumorigenesis in BALB/c nude mice. Circ_0058063 was significantly overexpressed in BC tissues. The downregulation of circ_0058063 impaired BC cell proliferation and migration ability but improved cell apoptosis ability. Circ_0058063 repressed miR-145-5p, which inhibited the expression of CDK6. Downregulation of circ_0058063 or miR-145-5p transfection contributed to more cells arresting in G0/G1 stage. MiR-145-5p suppressed cell growth and migration ability in BC, whereas CDK6 exerted the opposite influence on these cellular events. In vivo experiment also indicated that tumor development in BALB/c nude mice was repressed remarkably when circ_0058063 was downregulated. Circ_0058063 acted as a sponge of miR-145-5p to promote BC progression by regulating CDK6 expression, which provided some potential targets for BC treatment.

CircRNA circ_0067934 silencing inhibits the proliferation, migration and invasion of NSCLC cells and correlates with unfavorable prognosis in NSCLC.

Circular RNAs are a subgroup of non-coding RNAs and generated by a mammalian genome. The purpose of this study was to investigate the clinical significance, biological function and molecular mechanism of circ_0067934 in human non-small cell lung cancer (NSCLC). We assayed expression level of circ_0067934 in NSCLC tissues and cell lines by Real-time PCR. The associations of circ_0067934 expression with clinicopathologic features and overall survival of patients with NSCLC were statistically analyzed. Biological functions of circ_0067934 were analyzed using MTT and transwell migration and invasion assays in vitro. The expression of EMT-related mRNAs and proteins was assayed using Real-time PCR and Western blot. We found that circ_0067934 expression was significantly increased in NSCLC tissues and cell lines. High circ_0067934 expression was significantly associated with TNM stage (p=0.003), lymph node status (p=0.000), and distant metastasis (p=0.017). Moreover, Kaplan-Meier curves showed that higher expression of circ_0067934 led to a significantly poorer survival. Multivariate Cox proportional hazards analysis suggested that circ_0067934 was an independent poor prognostic factor for patients with NSCLC. In vitro assay indicated that down-regulation of circ_0067934 could suppress NSCLC cells proliferation, migration, and invasion. Mechanistic analysis showed that aberrant circ_0067934 expression could modulate the expression levels of markers of epithelial-to-mesenchymal transition. Our data suggested that circ_0067934 functioned as an oncogenic circular RNA in NSCLC, which provided a potential prognostic biomarker and therapeutic target for NSCLC.

Downregulation of circ_008018 protects against cerebral ischemia–reperfusion injury by targeting miR-99a

Circular RNAs (circRNAs) are highly expressed in eukaryotic cells and regulate physiological and pathophysiological processes. However, the role of circRNAs in cerebral ischemia–reperfusion (I/R) injury remains largely unknown. In this study, we found that circ_008018 level was higher in the cortical tissue of mice with middle cerebral artery occlusion as compared to those in the sham group 24 h after reperfusion. Knockdown of circ_008018 attenuated cerebral I/R-induced brain tissue damage and neurological deficits in mice by inducing microRNA miR-99a overexpression. The decreased phosphorylation of Akt and glycogen synthase kinase 3β caused by I/R was partly reversed by circ_008018 silencing or miR-99a overexpression. Taken together, these results provide new insight into the mechanisms of apoptosis resulting from cerebral I/R injury and suggest that targeted inhibition of circ_008018 can protect against subsequent neurological damage.