Circular RNA hsa_circ_0000073 contributes to osteosarcoma cell proliferation, migration, invasion and methotrexate resistance by sponging miR-145-5p and miR-151-3p and upregulating NRAS.
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ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC7425447 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background:Emerging evidence has revealed that circular RNAs (circRNAs) participated in hepatocellular carcinoma (HCC) development. However, the roles of most circRNAs have not been studied. Methods:CircZNF609, miR-342-3p and RAP2C expressions were assessed by qPCR or Western blot. Loss-of-function experiments were performed using si-circZNF609 transfection, followed by CCK-8 assay, flow cytometry, wound healing assay and transwell assay. Informatic tools and rescue experiments were carried out to investigate the underlying mechanisms. Results:We showed that circZNF609 was overexpressed in HCC tissues and cells, as well as associated with poor clinical characteristics. Depletion of circZNF609 restrained HCC cell viability, migration and invasion while enhanced cell apoptosis. As to mechanism, miR-342-3p was sponged by circZNF609, and RAP2C was targeted by miR-342-3p. The effects on HCC cells induced by si-circZNF609 could be reversed by miR-342-3p inhibitor or RAP2C. In vivo, circZNF609 knockdown inhibited tumorigenesis of HCC mice, confirming the findings in vitro. Conclusion:CircZNF609 was highly expressed in HCC tissues and driven HCC progression by sponging miR-342-3p and upregulating RAP2C. This study may provide new potential therapeutic targets for HCC treatment.
| S-EPMC7414977 | biostudies-literature
Project description:PurposeOsteosarcoma (OS) is the most common primary bone tumor, with high morbidity in infants and adolescents. Long noncoding RNA LINC00313 has been found to modulate papillary thyroid cancer tumorigenesis and to be dysregulate in lung cancer. However, the role of LINC00313 in OS has not yet been addressed.Materials and methodsWe evaluated mRNA and protein expression using real-time quantitative PCR and Western blotting. Cell proliferation was evaluated using MTT; apoptosis and autophagy were assessed with flow cytometry, Western blotting, and/or GFP-LC3 assay. Transwell assay was conducted to measure cell migration and invasion. Potential target sites for LINC00313 and miR-342-3p were predicted with starBase v.2.0 and TargetScan Human, and verified using luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down assay. In vivo, xenogeneic tumors were induced with U2OS and MG-63 cells, separately.ResultsLINC00313 was upregulated and miR-342-3p was downregulated in OS tissues and cells. High expression of LINC00313 was associated with shorter overall survival. FOSL2 downregulation and miR-342-3p overexpression suppressed cell proliferation and migratory and invasive abilities while promoting apoptosis and autophagy, all of which were consistent with the effects of LINC00313 knockdown. miR-342-3p, sponged by LINC00313, inversely modulated FOSL2 by targeting MG-63 cells, and FOSL2 expression was positively controlled by LINC00313. LINC00313 knockdown suppressed tumor growth in vivo.ConclusionLINC00313 is upregulated in OS, and LINC00313 knockdown plays a vital anti-tumor role in OS cell progression through a miR-342-3p/FOSL2 axis. Our study suggests that LINC00313 may be a novel, promising biomarker for diagnosis and prognosis of OS.
| S-EPMC7214116 | biostudies-literature
Project description:BACKGROUND:As a subclass of noncoding RNAs, circular RNAs (circRNAs) have been demonstrated to play a critical role in regulating gene expression in eukaryotes. Recent studies have revealed the pivotal functions of circRNAs in cancer progression. However, little is known about the role of circTADA2A, also named hsa_circ_0043278, in osteosarcoma (OS). METHODS:CircTADA2A was selected from a previously reported circRNA microarray comparing OS cell lines and normal bone cells. QRT-PCR was used to detect the expression of circTADA2A in OS tissue and cell lines. Luciferase reporter, RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were performed to confirm the binding of circTADA2A with miR-203a-3p. OS cells were stably transfected with lentiviruses, and Transwell migration, Matrigel invasion, colony formation, proliferation, apoptosis, Western blotting, and in vivo tumorigenesis and metastasis assays were employed to evaluate the roles of circTADA2A, miR-203a-3p and CREB3. RESULTS:Our findings demonstrated that circTADA2A was highly expressed in both OS tissue and cell lines, and circTADA2A inhibition attenuated the migration, invasion and proliferation of OS cells in vitro as well as tumorigenesis and metastasis in vivo. A mechanistic study revealed that circTADA2A could readily sponge miR-203a-3p to upregulate the expression of CREB3, which was identified as a driver gene in OS. Furthermore, miR-203a-3p inhibition or CREB3 overexpression could reverse the circTADA2A silencing-induced impairment of malignant tumor behavior. CONCLUSIONS:CircTADA2A functions as a tumor promoter in OS to increase malignant tumor behavior through the miR-203a-3p/CREB3 axis, which could be a novel target for OS therapy.
| S-EPMC6444890 | biostudies-literature
Project description:Circular RNAs (circRNAs) play critical regulatory roles in cancer biological processes. Nevertheless, the contributions and underlying mechanisms of circRNAs to pancreatic ductal adenocarcinoma (PDAC) remain largely unexplored. Dysregulated circRNAs between cancerous tissues and matched adjacent normal tissues were identified by circRNA microarray in PDAC. The biological effect of hsa_circ_007367 both in vitro and in vivo was demonstrated by gain- and loss-of-function experiments. Further, dual-luciferase reporter and RNA pull-down assays were performed to confirm the interaction among hsa_circ_007367, miR-6820-3p, and Yes-associated protein 1 (YAP1). The expression of hsa_circ_007367 and YAP1 were detected by in situ hybridization (ISH) and immunohistochemistry (IHC) using tissue microarray (TMA) in 128 PDAC samples. We first identified that a novel circRNA, hsa_circ_0007367, was markedly upregulated in PDAC tissues and cells. Functionally, in vivo and in vitro data indicated that hsa_circ_0007367 promotes the proliferation and metastasis of PDAC. Mechanistically, we confirmed that hsa_circ_0007367 could facilitate the expression of YAP1, a well-known oncogene, by sponging miR-6820-3p, which function as a tumor suppresser in PDAC cells. The results of ISH and IHC demonstrated that hsa_circ_0007367 and YAP1 were upregulated in PDAC tissues. Furthermore, clinical data showed that higher hsa_circ_0007367 expression was correlated with advanced histological grade and lymph node metastasis in PDAC patients. In conclusion, our findings reveal that hsa_circ_0007367 acts as an oncogene via modulating miR-6820-3p/YAP1 axis to promote the progression of PDAC, and suggest that hsa_circ_0007367 may serve as a potential therapeutic target for treatment of PDAC.
| S-EPMC9411600 | biostudies-literature
Project description:BackgroundCircular RNAs (circRNAs) have displayed important roles in the development and progression of various cancers. However, the functions of the majority of circRNAs in osteosarcoma (OS) remain unknown.MethodsCircular RNA microarray analysis was performed in three OS cell lines (Saos-2, U2OS and MG63) and normal vascular endothelial cells. The co-differentially expressed circRNAs (CDECs) were identified in OS cell lines with the criterion of FDR (false discovery rate) < 0.05 and |fold change (FC)|> 2. Quantitative real-time PCR was used to validate the expression levels of selected CDECs. A series of functional assays, including MTT assay, flow cytometry and transwell assay were conducted in OS cells. The interaction between circRNA and miRNAs was confirmed by luciferase reporter assay and RNA immunoprecipitation assay.ResultsA total of 241 CDECs, including 75 upregulated and 166 downregulated CDECs, were identified in three OS cell lines compared with normal vascular endothelial cells. PCR validation showed that hsa_circ_0000704, hsa_circ_0001017 and hsa_circ_0005035 were all highly expression in the three OS cell lines, compared with osteoblast cell lines (HECC, hFOB1.19 and HFF-1). Functionally, overexpression of circ_0001017 significantly promoted the cell proliferation, migration and invasion and decreased apoptosis in U2OS cells. Knockdown of circ_0001017 obtained the opposite results. Circ_0001017 may downregulate miR-145-5p through direct binding. Furthermore, the expression of miR-145-5p was negatively regulated by circ_0001017 in OS cells. In addition, further functional studies indicated that miR-145-5p inhibitor eliminated the effects caused by si-circ_0001017 in OS cells.ConclusionsIn conclusion, our study suggested that circ_0001017 may be a novel oncogenic factor during the progression and development of OS by targeting miR-145-5p.
| S-EPMC8962139 | biostudies-literature
Project description:In recent years, the mechanism of cancer research has become hotspots of life science and medicine, especially due to the rapid development of molecular medicine and bioinformatics research. Similarly, the molecular mechanism also has received increasing attention in osteosarcoma (OS) research. Also, a considerable amount of research confirmed that circular RNAs (circRNAs) could regulate cancer cell growth and metastasis. This study aimed to explore the effect of a circRNA, circCCDC66, on OS and reveal its potential molecular mechanism. High circCCDC66 expression level was found in OS patient-derived tissue samples and OS cell lines by qRT-PCR. The abilities cell proliferation and metastatic of U2OS and SW1353 cells were then assessed by Cell Counting Kit-8 and transwell assay, respectively. The interaction between circCCDC66 and its target miRNAs were verified by the dual-luciferase reporter assay. Through functional experiments, we found that circCCDC66 knockdown promoted the inhibition of cell proliferation and metastatic of OS cell lines. From mechanistic perspective, circCCDC66 upregulated PTP1B by sponging miR-338-3p. Collectively, our findings demonstrated that circCCDC66 contributed to malignant behaviors of OS cells by miR-338-3p/PTP1B pathway, which suggested circCCDC66/miR-338-3p/PTP1B axis might be a potential therapeutic target.
| S-EPMC7439191 | biostudies-literature
Project description:Circular RNAs (circRNAs) act crucial roles in the progression of multiple malignancies including osteosarcoma (OS). But, the underlying mechanisms by which hsa_circ_0017311 (circCNST) contributes to the tumorigenesis of OS remain poorly understood. Our present study aimed to explore the role and mechanisms of circCNST in OS tumorigenesis. The differentially expressed circRNAs were identified by the Gene Expression Omnibus database. The association of circCNST with clinicopathological features and prognosis in patients with OS was analyzed by RNA fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (PCR) analysis. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation assays, and a xenograft tumor model were conducted to assess the role of circCNST in OS cells in vitro and in vivo. CircCNST-specific binding with miR-421 was confirmed by FISH, luciferase gene report, and RNA immunoprecipitation assays. As a result, we found that the expression levels of circCNST were dramatically increased in OS tissues and cell lines as compared with the adjacent normal tissues, and it was associated with tumor size and poor survival in OS patients. Knockdown of circCNST repressed cell viability, colony formation, and xenograft tumor growth, while restored expression of circCNST reversed these effects. Furthermore, circCNST was colocalized with miR-421 in the cytoplasm and acted as a sponge of miR-421, which attenuated circCNST-induced proliferation-promoting effects in OS cells by targeting SLC25A3. In conclusion, our findings demonstrate that circCNST promotes the tumorigenesis of OS cells by sponging miR-421, and provides a potential biomarker for patients with OS.
| S-EPMC7563816 | biostudies-literature
Project description:Background Cervical cancer is a fatal burden for women. Circular RNAs (circRNAs) are important regulators in cancer development. Our study aimed to investigate the function and action mechanism of a novel circRNA, circ_0084927, in cervical cancer. Methods The expression of circ_0084927, miR-142-3p and ADP-ribosylation factor-like protein 2 (ARL2) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). For functional analyses, cell proliferation was assessed using cell counting kit-8 (CCK-8) assay. Cell cycle distribution was monitored by flow cytometry assay. Cell migration and cell invasion were evaluated by transwell assay. The interaction between miR-142-3p and circ_0084927 or ARL2 was predicted by the bioinformatics analysis and validated by dual-luciferase reporter assay and RNA immunoprecipitation assay (RIP) assay. The expression of ARL2 at the protein level was detected by Western blot. Animal tumor formation assay was performed to monitor the tumorigenicity of circ_0084927 in vivo. Results The expression of circ_0084927 and ARL2 was enhanced in cervical cancer tissues and cells, while the expression of miR-142-3p was opposite to them. Circ_0084927 knockdown significantly blocked cervical cancer cell proliferation, migration and invasion and induced cell cycle arrest. MiR-142-3p was targeted by circ_0084927, and miR-142-3p inhibition reversed the effects of circ_0084927 knockdown. Besides, miR-142-3p bound to ARL2, and the inhibitory effects of miR-142-3p restoration on cell proliferation, cycle, migration and invasion were counteracted by ARL2 overexpression. More importantly, circ_0084927 upregulated ARL2 expression by sponging miR-142-3p. Circ_0084927 knockdown retarded tumor growth in vivo by regulating miR-142-3p and ARL2. Conclusion Circ_0084927 accelerated the progression of cervical cancer partly by mediating the miR-142-3p/ARL2 axis.
| S-EPMC7532307 | biostudies-literature
Project description:BackgroundCervical cancer (CC) is one of the most common malignancies affecting female worldwide. Long non-coding RNAs (lncRNAs) are increasingly indicated as crucial participants and promising therapeutic targets in human cancers. The main objective of this study was to explore the functions and mechanism of LINC00885 in CC.MethodsRT-qPCR and western blot were used to detect RNA and protein levels. Functional and mechanism assays were respectively done for the analysis of cell behaviors and molecular interplays.ResultsLong intergenic non-coding RNA 885 (LINC00885) was discovered to be upregulated in CC tissues and cell lines through bioinformatics analysis and RT-qPCR. Overexpression of LINC00885 promoted proliferation and inhibited apoptosis, whereas its silence exerted opposite effects. The cytoplasmic localization of LINC00885 was ascertained and furthermore, LINC00885 competitively bound with miR-3150b-3p to upregulate BAZ2A expression in CC cells. Rescue assays confirmed that LINC00885 regulated CC proliferation and apoptosis through miR-3150b-3p/BAZ2A axis. Finally, we confirmed that LINC00885 aggravated tumor growth through animal experiments.ConclusionsLINC00885 exerted oncogenic function in CC via regulating miR-3150b-3p/BAZ2A axis. These findings suggested LINC00885 might serve as a potential promising therapeutic target for CC patients.
| S-EPMC8744347 | biostudies-literature
Project description:BackgroundLong non-coding RNAs (lncRNAs) have been identified as crucial regulatory factors in the occurrence and progression of osteosarcoma.MethodsQuantitative real-time polymerase chain reaction was used for detecting small nucleolar RNA host gene 4 (SNHG4) and miR-377-3p in osteosarcoma cells and tissues. Kaplan-Meier method was applied for evaluating the association between SNHG4 expression and the overall survival of osteosarcoma patients. CCK8, EdU, flow cytometry, and transwell assay were performed to examine the cell proliferation, apoptosis, cycle, and migration of osteosarcoma cells.ResultsIn our study, we found that lncRNA SNHG4 was highly expressed in osteosarcoma tissues and cell lines. Additionally, the SNHG4 expression was related to distant metastasis, TNM stage, and survival of osteosarcoma patients. Through SNHG4 knockdown, the proliferation of osteosarcoma cells was considerably restrained and the cell apoptosis was induced in vivo and in vitro. Moreover, downregulated SNHG4 inhibited the cell migration and epithelial-mesenchymal transition in HOS and MG63 cells. In mechanism, we found that SNHG4 acts as a competing endogenous RNA to sponge miR-377-3p, which is downregulated in osteosarcoma. Our results showed that there is a negative correlation between SNHG4 and miR-377-3p expression in osteosarcoma patients.ConclusionTaken together, SNHG4 promotes cell proliferation and migration by sponging miR-377-3p in osteosarcoma.
| S-EPMC7434752 | biostudies-literature