CircRNA circ_0006677 Inhibits the Progression and Glycolysis in Non-Small-Cell Lung Cancer by Sponging miR-578 and Regulating SOCS2 Expression.
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ABSTRACT:
SUBMITTER: Yang B
PROVIDER: S-EPMC8155686 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lung adenocarcinoma (LUAD) is a subtype of lung cancer with a high incidence and mortality all over the world. In recent years, circular RNAs (circRNAs) have been verified to be a novel subtype of noncoding RNAs that exert vital functions in various cancers. Our research was designed to investigate the role of circ_0018414 in LUAD. We first observed that circ_0018414 was downregulated in LUAD tissues and cells. Also, low expression of circ_0018414 predicted unfavorable prognosis of LUAD patients. Then, upregulation of circ_0018414 repressed cell proliferation and stemness, while promoting cell apoptosis, in LUAD. Moreover, circ_0018414 overexpression enhanced the expression of its host gene, dickkopf WNT signaling pathway inhibitor 1 (DKK1), therefore inactivating the Wnt/β-catenin pathway. Additionally, circ_0018414 could sponge miR-6807-3p to protect DKK1 mRNA from miR-6807-3p-induced silencing, leading to DKK1 upregulation in LUAD cells. Finally, rescue assays proved that circ_0018414 inhibited the progression of LUAD via the miR-6807-3p/DKK1 axis-inactivated Wnt/β-catenin pathway. The findings in our work indicated circ_0018414 as a tumor inhibitor in LUAD, which might provide a new perspective for LUAD treatment.
| S-EPMC7868730 | biostudies-literature
Project description:Circular RNAs (circRNAs), one kind of noncoding RNAs, can interact with miRNA and transcription factors to regulate gene expression. However, little is known on which circRNA is crucial for the pathogenesis of hepatocellular carcinoma (HCC). CircRNA expression profile was analyzed by a microarray. Regulatory gene targets were predicted by bioinformatics analysis and validated by luciferase assay. Their expression was determined by qRT-PCR and Western blotting. DNA methylation was determined by methylation-specific PCR. Gene knockdown and overexpression were mediated by lentivirus-mediated shRNA and transfection with plasmids for cDNA expression, respectively. MTT assay, wound-healing assay, transwell invasion assay, and flow cytometry were used to determine malignant behaviors of HCC cells. HCC xenograft mouse model was used to determine the in vivo effects of circRNA-5692. CircRNA-5692 expression was downregulated in HCC tissues, and circRNA-5692 overexpression attenuated the malignant behaviors of HCC cells. Bioinformatics predicted that circRNA-5692 interacted with miR-328-5p, which targeted the DAB2IP mRNA. Actually, miR-328-5p promoted the malignant behaviors of HCC cells, while DAB2IP had opposite effects. Moreover, circRNA-5692 overexpression inhibited the growth of xenograft HCC tumors in vivo by decreasing miR-328-5p expression to enhance DAB2IP expression. In conclusion, the circRNA-5692-miR-328-5p-DAB2IP regulatory pathway inhibits the progression of HCC. Our findings may provide potential new targets for the diagnosis and therapy of HCC.
| S-EPMC6881381 | biostudies-literature
Project description:Strategies targeted vascular endothelial growth factor (VEGF)-dependent osteosarcoma progression are limited although important progress has been made in illustrating the mechanisms. Here we identified circ_001621 as one of the significantly upregulated circular RNAs (circRNAs) by circRNAs microarrays. We found that patients with high circ_001621 expression had a shorter survival time. Moreover, we found several potential sponge micro RNAs (miRNA) of circ_001621 with Circular RNA Interactome database. Among the candidate sponge, we elucidated the association of circ_001621 and miR-578. In addition, we demonstrated that miR-578 targeted circ_001621 directly. Functionally, we set up the experimental system to investigate the effects of circ_001621/miR-578/VEGF interaction in vitro and in vivo. Results indicated circ_001621-promoted osteosarcoma proliferation and migration via attenuating the inhibition of cyclin-dependent kinase 4 (CDK4) and matrix metallopeptidase 9 (MMP9) by miR-578, respectively. Nude mice experiment was further performed to estimate the promotion of metastasis by circ_001621. The present study evaluated the mechanisms underlying circ_001621 enhanced osteosarcoma progression and provided novel therapeutic targets for advanced osteosarcoma.
| S-EPMC6944700 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC).Materials and methodsqRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10.ResultsCircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10.ConclusionsCircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients.
| S-EPMC7780627 | biostudies-literature
Project description:BackgroundCirc-ITCH is a circRNA generated from several exons of itchy E3 ubiquitin protein ligase (ITCH) and tumor suppressor served as a sponge for certain miRNAs targeting their parental transcripts of ITCH. However, the role of circ-ITCH in bladder cancer (BCa) was not reported. In the present study, we investigated the role of circ-ITCH in BCa.MethodsQuantitative real-time PCR was used to detect the expression of circ-ITCH and survival analysis was adopted to explore the association between circ-ITCH expression and the prognosis of BCa. BCa cells were stably transfected with lentivirus approach and cell proliferation, migration, invasion, cell cycle and cell apoptosis, as well as tumorigenesis in nude mice were performed to assess the effect of circ-ITCH in BCa. Biotin-coupled probe pull down assay, Biotin-coupled miRNA capture, Fluorescence in situ hybridization and Luciferase reporter assay were conducted to confirm the relationship between the circ-ITCH and the microRNA.ResultsIn the present study, we found that circ-ITCH, is down-regulated in BCa tissues and cell lines. BCa patients with low circ-ITCH expression had shortened survival. Enforced- expression of circ-ITCH inhibited cells proliferation, migration, invasion and metastasis both in vitro and in vivo. Mechanistically, we demonstrated that circ-ITCH up-regulates the expression of miR-17 and miR-224 target gene p21 and PTEN through 'sponging' miR-17 and miR-224, which suppressed the aggressive biological behaviors of BCa.Conclusionscirc-ITCH acts as a tumor suppressor by a novel circ-ITCH/miR-17, miR-224/p21, PTEN axis, which may provide a potential biomarker and therapeutic target for the management of BCa.
| S-EPMC5793418 | biostudies-literature
Project description:Background:Evidence has been shown that circular RNAs (circRNAs) play a vital role during the development of ovarian cancer. However, the mechanism by which circEXOC6B regulates tumorigenesis of ovarian cancer remains unknown. Thus, this study aimed to investigate the role of circEXOC6B during the progression of ovarian cancer. Materials and Methods:The dual-luciferase reporter system assay was used to determine the interaction between circEXOC6B, miR-421 and RUS1 in ovarian cancer, respectively. CCK8 and colony formatting were used to evaluate cell proliferation. Meanwhile, the expressions of RSU1, PINCH1 and ILK in SKOV3 cells were detected with Western blot. Results:Downregulation of circEXOC6B markedly promoted the proliferation and invasion in A2780 cells. In contrast, upregulation of circEXOC6B significantly inhibited the proliferation and invasion in SKOV3 cells. Moreover, overexpression of circEXOC6B obviously induced the apoptosis of SKOV3 cells. Furthermore, luciferase reporter assay identified that miR-421 was the potential miRNA binding of circEXOC6B, and RUS1 was the potential binding target of miR-421. Mechanism analysis indicated that upregulation of circEXOC6B increased the level of RUS1 by acting as a competitive "sponge" of miR-421. Conclusion:In this study, we found that circEXOC6B suppressed the growth of ovarian cancer cells through upregulating RSU1 partially via sponging miR-421. Therefore, circEXOC6B might be a potential target for the treatment of ovarian cancer.
| S-EPMC7443403 | biostudies-literature
Project description:Circular RNAs (circRNAs) have emerged as essential regulators and biomarkers of various cancers. However, the effects of a novel circRNA termed circGRAMD1B in human gastric cancer (GC) remain unclear. A microarray was used to screen circRNA expression in GC. Quantitative real-time PCR was used to detect the expression of circGRAMD1B. Gain- and loss- of-function experiments were performed to investigate the biological functions of circGRAMD1B in vitro and vivo. Bioinformatics analysis, fluorescence in situ hybridization, dual-luciferase reporter assay, RNA immunoprecipitation, RNA pull-down assay, and rescue experiments were conducted to confirm the underlying mechanisms of competitive endogenous RNAs (ceRNAs). We screened differentially expressed circRNAs and found that circGRAMD1B expression was downregulated in GC tissues and cell lines. Functionally, circGRAMD1B acted as an anti-oncogene and inhibited the proliferation, migration, and invasion abilities of GC cells. Then, we verified that circGRAMD1B served as a sponge that targeted miR-130a-3p in GC cells; circGRAMD1B alleviated GC cell proliferation, migration, and invasion by targeting miR-130a-3p. A mechanistic analysis showed that PTEN and p21 were involved in circGRAMD1B/miR-130a-3p axis-inhibited GC tumorigenesis. Our findings suggest that circGRAMD1B plays an important role in GC progression by regulating miR-130a-3p-PTEN/p21, which may provide a potential biomarker and therapeutic target for GC.
| S-EPMC6874462 | biostudies-literature
Project description:Circular RNAs (circRNAs) have been demonstrated to play important roles in cancer progress. However, the roles in hepatocellular carcinoma (HCC) are still unclear. Here, we found has_circRNA_001306 (circ_1306) was up-regulated in HCC tissues and cell lines. Knockdown the expression circ_1306 significantly suppressed HCC cell proliferation and induced the cell apoptosis in vitro and in vivo. Furthermore, we identified circ_1306 could up-regulate the expression of CDK16 by sponging miR-584-5p. The expression of miR-584-5p was decreased, and the expression of CDK16 was increased in HCC tissues and cell lines. Meanwhile, either knockdown of miR-584-5p or overexpression of CDK16 could suppress the HCC cell proliferation. In vivo, overexpression of miR-584-5p or knockdown of circ_1306 could inhibit the expression of CDK16, and suppress tumour growth. Altogether, our findings suggested that circ_1306 could promoter HCC progress by miR-584-5p/CDK16 axis, which provided a novel marker for HCC diagnosis and treatment.
| S-EPMC7754030 | biostudies-literature
Project description:Background Pancreatic cancer is an extensively concerned human malignancy around the globe, yet the potential therapeutic target remains to be further determined. MicroRNA and LncRNA have been reported to be involved in progression of pancreatic cancer, while the biological role of microRNA-574-3p (miR-574-3p) and FAM66C in pancreatic cancer development is poorly investigated. Methods Quantitative real-time PCR (qPCR) analysis was employed to detect the expression of miR-574-3p and FAM66C in pancreatic normal or cancerous tissues and cells. The proliferative and apoptosis signaling molecules were also examined via qPCR and western blot separately. Additionally, cell proliferation and apoptosis assay were performed via CCK8, colony formation and Annexin V-FITC apoptosis assay. Interaction between miR-574-3p and FAM66C was interrogated by luciferase reporter assay and RNA immunoprecipitation. Even more, a pancreatic cancer xenograft mice assay was implemented to illustrate the coordinating role of miR-574-3p and FAM66C in pancreatic cancer proliferation. Results We found that levels of miR-574-3p were significantly higher in cancer tissues and cells compared to normal (P<0.05). Remarkably, the results indicated that depletion of miR-574-3p inhibited proliferation and promoted apoptosis of human pancreatic cancer cell lines. Additionally, FAM66C was demonstrated to interact with miR-574-3p and inhibit its expression. Significantly, FAM66C was proved to act as a tumor suppressor role via inhibiting cell proliferation and promoting cell apoptosis in pancreatic cancer. Moreover, FAM66C coordinated with miR-574-3p to regulate progression of xenograft tumor in the nude mice. Conclusions FAM66C-miR-574-3p axis mediates progression of pancreatic and might be the promising therapeutic target for pancreatic cancer patients.
| S-EPMC8798657 | biostudies-literature
Project description:Background:Breast cancer (BC) is the most common malignancy among women. Emerging studies have demonstrated that circular RNA (circRNA) zinc finger RNA binding protein (circZFR) serves as a crucial regulator in many human cancers. However, the role and mechanism of circZFR in BC tumorigenesis remain unclear. Methods:The levels of circZFR, miR-578 and hypoxia-inducible factor 1? (HIF1A) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, colony formation, apoptosis, migration and invasion capacities in vitro were determined by using the Cell Counting Kit-8 (CCK-8), standard colony formation, flow cytometry and transwell assays, respectively. Glucose uptake, lactate product and adenosine triphosphate (ATP) levels of cells in vitro were measured using the commercial human assay kits. Targeted relationships among circZFR, miR-578 and HIF1A in BC cell lines were verified by dual-luciferase reporter and RNA pulldown assays. Animal studies were performed to assess the effect of circZFR on tumor growth in vivo. Results:Our data indicated that circZFR was overexpressed in BC tissues and cells, and the increased circZFR level predicted poor prognosis of BC patients. CircZFR silencing or miR-578 overexpression repressed BC cell viability, colony formation, migration, invasion, and glycolysis and enhanced cell apoptosis in vitro. CircZFR silencing also hampered tumor growth in vivo. Mechanistically, circZFR acted as a sponge of miR-578, and circZFR silencing hindered BC cell malignant behaviors by miR-578. HIF1A was a functional target of miR-578 in regulating BC cell viability, colony formation, migration, invasion, glycolysis and apoptosis in vitro. Furthermore, circZFR modulated HIF1A expression through sponging miR-578. Conclusion:Our findings first identified that the silencing of circZFR suppressed BC malignant progression in vitro via the regulation of the miR-578/HIF1A axis, providing evidence for the crucial involvement of circZFR in BC pathogenesis.
| S-EPMC7437024 | biostudies-literature