Circ_0005615 promotes cervical cancer cell growth and metastasis by modulating the miR-138-5p/KDM2A axis

Cervical cancer (CC) is a highly fatal gynecological malignancy due to its high metastasis and recurrence rate. Circular RNA (circRNA) has been regarded as a regulator of CC. However, the underlying molecular mechanism of circ_0005615 in CC remains unclear. The levels of circ_0005615, miR-138-5p, and lysine demethylase 2A (KDM2A) were measured using qRT-PCR or western blot. Cell proliferation was assessed by Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, and colony formation experiments. Cell invasion and migration were tested by transwell assay and wound healing assay. Flow cytometry and Caspase-Glo 3/7 Assay kit were used to analyze cell apoptosis. The expression of proliferation-related and apoptosis-related markers was detected by western blot. The binding relationships among circ_0005615, miR-138-5p, and KDM2A were verified by dual-luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was applied to detect the effect of circ_0005615 in vivo. Circ_0005615 and KDM2A were upregulated, while miR-138-5p was downregulated in CC tissues and cells. Circ_0005615 knockdown retarded cell proliferation, migration, and invasion, while promoting apoptosis. Besides, circ_0005615 sponged miR-138-5p, and miR-138-5p could target KDM2A. miR-138-5p inhibitor reversed the regulation of circ_0005615 knockdown on CC cell growth and metastasis, and KDM2A overexpression also abolished the inhibitory effect of miR-138-5p on CC cell growth and metastasis. In addition, we also discovered that circ_0005615 silencing inhibited CC tumor growth in vivo. Circ_0005615 acted as a tumor promoter in CC by regulating the miR-138-5p/KDM2A pathway.     

Circ_0026579 alleviates LPS-induced WI-38 cells inflammation injury in infantile pneumonia

Circular RNA (circRNA) represents an important regulator in infantile pneumonia progression. To clarify the role of circ_0026579 in this disease, LPS was used to treat WI-38 cells to mimic inflammation injury. The levels of inflammatory factors were determined by ELISA assay. Cell proliferation and apoptosis were measured by MTT assay, EdU staining and flow cytometry. The protein levels of cyclinD1, cleaved-caspase-3 and insulin-like growth factor 2 (IGF2) were examined using Western blot analysis. Cell oxidative stress was assessed by detecting MDA level and SOD activity. The expression of circ_0026579, miR-24-3p and IGF2 were analyzed using quantitative real-time PCR, and the interaction between miR-24-3p and circ_0026579 or IGF2 was confirmed by dual-luciferase reporter assay and RIP assay. LPS induced inflammation in WI-38 cells. Circ_0026579 expression was promoted in LPS-induced WI-38 cells, and its knockdown alleviated LPS-induced WI-38 cells inflammation. MiR-24-3p was sponged by circ_0026579, and its expression was reduced by LPS. MiR-24-3p inhibitor reversed the regulation of circ_0026579 knockdown on LPS-induced WI-38 cells inflammation. IGF2 was targeted by miR-24-3p, and its expression could be enhanced by LPS. MiR-24-3p relieved the inflammation of WI-38 cells which could be abolished by IGF2 overexpression. Circ_0026579 positively regulated IGF2 expression through sponging miR-24-3p. Circ_0026579 knockdown alleviated LPS-induced WI-38 cells inflammation by miR-24-3p/IGF2 axis, suggesting that circ_0026579 might contribute to infantile pneumonia progression.     

Circ_0011058 facilitates proliferation,angiogenesis and radioresistance in papillary thyroid cancer cells by positively regulating YAP1 via acting as miR-335-5p sponge

BackgroundCircular RNAs (circRNAs) are reported to be associated with multiple biological processes in human cancers. However, there are still numerous circRNAs whose functions remain unclear. The aim of this study was to investigate the role of circ_0011058 in papillary thyroid cancer (PTC).MethodsQuantitative real-time PCR (qPCR) was utilized to detect the expression of circ_0011058, microRNA-335-5p (miR-335-5p) and Yes-associated Protein 1 (YAP1). Cell proliferation was detected using cell counting kit-8 (CCK-8) assay and EdU assay. Cell apoptosis was detected by flow cytometry assay. Angiogenesis ability was assessed using tube formation assay. The expression of angiogenesis-related proteins and YAP1 protein was detected by western blot. Radioresistance was examined using colony formation assay. The binding relationship between miR-335-5p and circ_0011058 or YAP1 was verified by dual-luciferase reporter assay, pull-down assay and RIP assay. Xenograft models were constructed to ensure the role of circ_0011058.ResultsCirc_0011058 expression was aberrantly elevated in PTC tissues and cells. The downregulation of circ_0011058 suppressed proliferation, angiogenesis and radioresistance in PTC cells. MiR-335-5p was defined as a target of circ_0011058, and miR-335-5p inhibition reversed the effects of circ_0011058 downregulation. In addition, YAP1 was a target of miR-335-5p, and circ_0011058 positively regulated YAP1 expression by targeting miR-335-5p. MiR-335-5p restoration inhibited proliferation, angiogenesis and radioresistance in PTC cells, while YAP1 overexpression abolished these effects. Animal study showed that circ_0011058 knockdown inhibited tumor growth in vivo.ConclusionCirc_0011058 promoted PTC cell proliferation, angiogenesis and radioresistance by upregulating YAP1 via acting as miR-335-5p sponge.     

Circ_0015756 promotes ovarian cancer progression via the miR-145–5p/PSAT1 axis

Circular RNA (circRNA) have been shown to exert vital functions in the pathological progressions of ovarian cancer (OC). Herein, this study aimed to investigate the role and mechanisms of circ_0015756 in OC progression. Levels of circ_0015756, microRNA (miR)? 145–5p and phosphoserine aminotransferase 1 (PSAT1) were detected using quantitative real-time polymerase chain reaction, Western blot or immunohistochemistry assays. Cell proliferation, apoptosis, migration and invasion were determined using cell counting kit-8, 5-Ethynyl-2′-Deoxyuridine (Edu) incorporation, flow cytometry, transwell and Western blot assays. The binding interaction between miR-145–5p and circ_0015756 or PSAT1 was confirmed by bioinformatics prediction and dual-luciferase reporter assay. Tumor formation assay in nude mice was performed to determine the tumor growth in vivo. Circ_0015756 was highly expressed in OC tissues and cells. Knockdown of circ_0015756 suppressed cancer cell growth, migration and invasion in vitro, as well as impeded tumor growth in vivo. In a mechanical study, circ_0015756 directly bound to miR-145–5p, and inhibition of miR-145–5p reversed the effects of circ_0015756 knockdown on OC cells. Moreover, miR-145–5p directly targeted PSAT1, and miR-145–5p weakened OC cell growth, migration and invasion via targeting PSAT1. Importantly, further studies confirmed that circ_0015756 could indirectly regulate PSAT1 expression via sponging miR-145–5p. In all, circ_0015756 accelerated OC tumorigenesis through regulating miR-145–5p/PSAT1 axis, providing a new therapeutic target for OC.     

Circ_0004712 promotes endometriotic epithelial cell proliferation,migration and invasion by regulating miR-488-3p/ROCK1 axis in vitro

Recent evidence indicates that circular RNAs (circRNAs) play crucial regulatory roles in the pathogenesis and development of endometriosis. Circ_0004712 was found to be differentially expressed in endometriosis. However, the detailed function and mechanism of circ_0004712 in endometriosis are still unclear. Quantitative real-time polymerase chain reaction and Western blot were used for the detection of circ_0004712, miR-488-3p and ROCK1 (Rho Associated Coiled-Coil Containing Protein Kinase 1) levels. In vitro experiments in endometrial endothelial cells were performed by cell counting kit-8, EdU, transwell, wound healing assays, and flow cytometry, respectively. The molecular mechanism of circ_0004712 function was investigated using bioinformatics target predication, dual-luciferase reporter, and RNA immunoprecipitation (RIP) assays. The expression of circ_0004712 was higher in endometriotic endometrial tissues and epithelial cells. Knockdown of circ_0004712 suppressed cell proliferation, migration, invasion, EMT process and induced apoptosis in ectopic endometrial epithelial cells in vitro. Mechanistically, circ_0004712 acted as a ceRNA to sponge miR-488-3p, thus elevating the expression of ROCK1, which was confirmed to be a target of miR-488-3p. Rescue experiments suggested that miR-488-3p inhibition reversed the inhibitory effects of circ_0004712 silencing on cell growth and metastasis. Moreover, miR-488-3p restoration restrained the proliferation and metastasis in ectopic endometrial epithelial cells, which were attenuated by ROCK1 overexpression. Circ_0004712 knockdown suppressed the proliferation and metastasis of ectopic endometrial epithelial cells via miR-488-3p/ROCK1 axis in vitro, suggesting a new insight into the pathogenesis of endometriosis.     

Circular RNA circ_0032962 promotes trophoblast cell progression as ceRNA to target PBX3 via sponging miR-326 in preeclampsia

Preeclampsia (PE) is the leading cause of maternal deaths in primipara. It is mainly characterized by defect migration and invasion of trophoblast cells. Circular RNAs (circRNAs) have been widely reported to be associated with PE progression. This study is designed to explore the role and mechanism of circ_0032962 on trophoblast cell behavior. Circ_0032962, microRNA-326 (miR-326), and Pre-B-cell leukemia homeobox 3 (PBX3) levels were measured by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability, migration, and invasion were measured by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), Colony formation, wound healing, and transwell assays. Protein levels of E-cadherin, Vimentin, N-cadherin, and PBX3 were examined by western blot assay. The binding relationship between miR-326 and circ_0032962 or PBX3 was predicted by circular RNA Interactome or Starbase and then verified by a dual-luciferase reporter assay. Circ_0032962 and PBX3 levels were declined in placenta tissues from preeclampsia patients, and miR-326 was elevated. Apart from that, circ_0032962 knockdown could suppress cell proliferation ability, migration, invasion, and epithelial-mesenchymal transition (EMT) in trophoblast cells. Mechanically, circ_0032962 could affect PBX3 expression through sponging miR-326. Circ_0032962 could contribute to trophoblast cell growth ability and metastasis partly by regulating the miR-326/PBX3 axis, providing a novel insight into the pathogenesis and treatment of PE.     

Circ_0023404 sponges miR-136 to induce HK-2 cells injury triggered by hypoxia/reoxygenation via up-regulating IL-6R

The significance of circular RNAs (circRNAs) is reported in various kidney diseases including acute kidney injury (AKI). Specific circRNAs have the capacity to function as novel indicators of AKI. Circ_0023404 exhibits an important role in several diseases. Nevertheless, the detailed biological role of circ_0023404 in AKI remains poorly known. The present study aimed to investigate the effect of circ_0023404 on renal ischaemia/reperfusion (I/R) injury in vitro. Here, we evaluated the function of circ_0023404 in HK-2 cells in response to hypoxia/reoxygenation (H/R). We established a cell AKI model induced by H/R in HK-2 cells. We found circ_0023404 was significantly increased in AKI. Then, we found loss of circ_0023404 increased cell growth, repressed apoptosis, reduced inflammatory factors secretion and oxidative stress generation in vitro. Besides, circ_0023404 sponged miR-136. miR-136 overturned the effects of circ_0023404 on HK-2 cell injury. We assumed IL-6 receptor (IL-6R) as a target of miR-136 and IL-6R was activated by circ_0023404 via sponging miR-136. In conclusion, we revealed circ_0023404 contributed to HK-2 cells injury stimulated by H/R via sponging miR-136 and activating IL-6R.     

MiR-20a-3p regulates TGF-β1/Survivin pathway to affect keratinocytes proliferation and apoptosis by targeting SFMBT1 in vitro

Psoriasis is a common immune-mediated chronic inflammatory skin disease characterized by abnormal keratinocyte proliferation, differentiation and apoptosis. However, the exact etiology and pathogenesis are still unclear. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. It has been demonstrated that Interleukin-22 (IL-22) plays vital role in T cell-mediated immune response by interacting with keratinocytes in the pathogenesis of psoriasis. The aim of our study was to explore the possible functional role of miR-20a-3p in psoriasis and in IL-22 induced keratinocyte proliferation. Here, we found that miR-20a-3p was down-regulated in psoriatic lesions and in HaCaT cells (human keratinocyte cell line) treated by IL-22 stimulation. Functional experiments showed that overexpression of miR-20a-3p in HaCaT cells suppressed proliferation and induced apoptosis while its knockdown promoted cell proliferation and reduces cell apoptosis. Mechanistically, SFMBT1 was identified as the direct target of miR-20a-3p by dual luciferase reporter assay. SFMBT1 knockdown was demonstrated to inhibit cell growth and induced apoptosis, which was consistent with the function of miR-20a-3p upregulation in HaCaT cells. In addition, results of western blot analysis showed that miR-20a-3p upregulation or SFMBT1 knockdown changed the protein expression levels of TGF-β1 and survivin. Our findings suggest that miR-20a-3p play roles through targeting SFMBT1 and TGF-β1/Survivin pathway in HaCaT cells, and loss of miR-20a-3p in psoriasis may contribute to hyperproliferation and aberrant apoptosis of keratinocytes.     

Circ_0058106 promotes proliferation,metastasis and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway through miR-185-3p in hypopharyngeal squamous cell carcinoma

Hypopharyngeal squamous cell carcinoma (HSCC) accounts 95% of hypopharyngeal cancer, which is characterized by high early metastasis rate and poor prognosis. It is reported that circular RNA is involved in the occurrence and development of cancer; however, the role of circRNA in hypopharyngeal cancer has little been investigated. We performed hypopharyngeal carcinoma circRNA microarray and qRT-PCR verification. The results showed circ_0058106 expression level was significantly upregulated in tumor tissues than in corresponding normal tissues. We found that circ_0058106 upregulation promoted proliferation, migration and invasion of HSCC cells, while knockdown of circ_0058106 inhibited proliferation, migration and invasion of HSCC cells both in vitro and in vivo. Bioinformatics predicted circ_0058106 may interact with miR-185-3p. We verified circ_0058106 directly bound miR-185-3p and downregulated miR-185-3p expression by using dual-luciferase reporter assay and qRT-PCR. Moreover, we proved circ_0058106 promoted HSCC cells tumorigenesis and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway via miR-185-3p. In conclusion, our findings firstly confirmed the carcinogenic effect of circ_0058106 in promoting HSCC cells tumorigenesis, metastasis, invasion and EMT process by regulating Wnt2b/β-catenin/c-Myc pathway through sponging miR-185-3p, indicating that circ_0058106 may be a new therapeutic target and prognostic marker for HSCC.Subject terms: Head and neck cancer, Head and neck cancer     

Silencing of circ_0000205 mitigates interleukin-1β-induced apoptosis and extracellular matrix degradation in chondrocytes via targeting miR-766-3p/ADAMTS5 axis

The aim of this study was to explore the role of hsa_circRNA_0000205 (circ_0000205) in chondrocyte injury in osteoarthritis (OA) and the underlying mechanism. Expression of circ_0000205, microRNA (miR)-766-3p and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5 was detected by quantitative real time (qRT)-polymerase chain reaction (PCR) and Western blot assays. Cell proliferation, apoptosis, and extracellular matrix (ECM) synthesis were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and 5-ethynyl-2-deoxyuridine assays, flow cytometry, and qRT-PCR and Western blot assays. The target relationship between miR-766-3p and circ_0000205 or ADAMTS5 was confirmed by luciferase reporter assay and RNA immunoprecipitation. IL-1β treatment could attenuate cell viability of primary chondrocytes and proliferating cell nuclear antigen (PCNA) and collagen II type alpha-1 (COL2A1) levels, and elevate apoptosis rate and cleaved caspase-3, ADAMTS5 and matrix metalloproteinase-13 (MMP13) levels, suggesting that IL-1β induced chondrocyte apoptosis and ECM degradation. Expression of circ_0000205 was up-regulated in OA tissues and IL-1β-induced primary chondrocytes, accompanied with miR-766-3p down-regulation and ADAMTS5 up-regulation. Knockdown of circ_0000205 could mitigate IL-1β-induced above effects and improve cell proliferation. Moreover, both depleting miR-766-3p and promoting ADAMTS5 could partially counteract circ_0000205 knockdown roles in IL-1β-cultured primary chondrocytes. Notably, circ_0000205 was verified as a sponge for miR-766-3p via targeting, and ADAMTS5 was a direct target for miR-766-3p. Silencing circ_0000205 could protect chondrocytes from IL-1β-induced proliferation reduction, apoptosis, and ECM degradation by targeting miR-766-3p/ADAMTS5 axis.     

Circ_0002984 induces proliferation,migration and inflammation response of VSMCs induced by ox-LDL through miR‑326-3p/VAMP3 axis in atherosclerosis

Atherosclerosis can result in multiple cardiovascular diseases. Circular RNAs (CircRNAs) have been reported as significant non-coding RNAs in atherosclerosis progression. Dysfunction of vascular smooth muscle cells (VSMCs) is involved in atherosclerosis. However, up to now, the effect of circ_0002984 in atherosclerosis is still unknown. Currently, we aimed to investigate the function of circ_0002984 in VSMCs incubated by oxidized low-density lipoprotein (ox-LDL). Firstly, our findings indicated that the expression levels of circ_0002984 were significantly up-regulated in the serum of atherosclerosis patients and ox-LDL-incubated VSMCs. Loss of circ_0002984 suppressed VSMC viability, cell cycle distribution and migration capacity. Then, we carried out ELISA assay to determine TNF-α and IL-6 levels. The data implied that lack of circ_0002984 obviously repressed ox-LDL–stimulated VSMC inflammation. Meanwhile, miR-326-3p, which was predicted as a target of circ_0002984, was obviously down-regulated in VSMCs treated by ox-LDL. Additionally, after overexpression circ_0002984 in VSMCs, a decrease in miR-326-3p was observed. Subsequently, miR-326-3p was demonstrated to target vesicle-associated membrane protein 3 (VAMP3). Therefore, we hypothesized that circ_0002984 could modulate expression of VAMP3 through sponging miR-326-3p. Furthermore, we confirmed that up-regulation of miR-326-3p rescued the circ_0002984 overexpressing-mediated effects on VMSC viability, migration and inflammation. Additionally, miR-326-3p inhibitor-mediated functions on VSMCs were reversed by knockdown of VAMP3. In conclusion, circ_0002984 mediated cell proliferation, migration and inflammation through modulating miR-326-3p and VAMP3 in VSMCs, which suggested that circ_0002984 might hold great promise as a therapeutic strategy for atherosclerosis.     

Circ_0025039 acts an oncogenic role in the progression of non-small cell lung cancer through miR-636-dependent regulation of CORO1C

Non-small cell lung cancer remains the leading cause of cancer-related death worldwide. Circular RNA plays vital roles in NSCLC progression. This study is designed to reveal the role of circ_0025039 in NSCLC cell malignancy. The RNA expression of circ_0025039, microRNA-636 (miR-636), and coronin 1C was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by Western blot analysis or immunohistochemistry assay. Cell proliferation, migration, invasion, tube formation ability, sphere formation capacity, and apoptosis were investigated by cell counting kit-8, 5-Ethynyl-29-deoxyuridine, transwell assay, tube formation assay, sphere formation assay, and flow cytometry analysis, respectively. Mouse model assay was conducted to reveal the effect of circ_0025039 silencing on tumor formation in vivo. The interaction between miR-636 and circ_0025039 or CORO1C was identified through dual-luciferase reporter and RNA pull-down assays. The expression of circ_0025039 and CORO1C was significantly increased, while miR-636 was decreased in NSCLC tissues and cells compared with controls. Circ_0025039 depletion repressed NSCLC cell proliferation, migration, invasion, tube-forming capacity, and sphere formation ability, but induced cell apoptosis. The neoplasm formation was repressed after circ_0025039 silencing. Additionally, circ_0025039 acted as a sponge for miR-636, which was found to target CORO1C. Importantly, the contribution of circ_0025039 to NSCLC progression was mediated by miR-636/CORO1C axis. Circ_0025039 silencing repressed NSCLC malignant progression by reducing CORO1C expression through miR-636, showing the possibility of circ_0025039 as a therapeutic target for NSCLC.

     

Circ_0003423 Alleviates ox-LDL-Induced Human Brain Microvascular Endothelial Cell Injury via the miR-589-5p/TET2 Network

Brain microvascular endothelial cells (BMECs) injury is one of the main causes of cerebrovascular diseases. Circular RNA (circRNA) has been found to be involved in the regulation of cerebrovascular diseases progression. However, the role and mechanism of circ_0003423 in cerebrovascular diseases is still unclear. In our study, oxidized low density lipoprotein (ox-LDL)-induced HBMEC-IM cells were used to construct cerebrovascular cell injury model in vitro. Quantitative real-time PCR was used to determine the expression levels of circ_0003423, miR-589-5p and Ten-eleven translocation 2 (TET2). The interactions between miR-589-5p and circ_0003423 or TET2 were confirmed by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Cell viability, angiogenesis and apoptosis were measured using cell counting kit 8 assay, tube formation assay and flow cytometry. Cell oxidative stress was evaluated by detecting the levels of reactive oxygen species and lactate dehydrogenase. The protein levels were examined by western blot analysis. Our results showed that circ_0003423 was a downregulated circRNA in ox-LDL-induced HBMEC-IM cells. In the terms of mechanism, circ_0003423 was found to be a sponge of miR-589-5p. Function analysis showed that circ_0003423 overexpression could relieve ox-LDL-induced HBMEC-IM cell injury, and this effect could be reversed by miR-589-5p mimic. In addition, TET2 was confirmed to be a target of miR-589-5p, and its overexpression could alleviate ox-LDL-induced HBMEC-IM cell injury. Moreover, the rescue experiments also confirmed that TET2 silencing could abolish the inhibition effect of anti-miR-589-5p on ox-LDL-induced HBMEC-IM cell injury. In summary, our data showed that circ_0003423 alleviated ox-LDL-induced HBMEC-IM cells injury through regulating the miR-589-5p/TET2 axis.

     

Long intergenic noncoding RNA 00641 inhibits breast cancer cell proliferation,migration, and invasion by sponging miR-194-5p

Long noncoding RNAs have an essential role in the tumorigenesis of breast cancer (BC). Nonetheless, the consequences of long intergenic noncoding RNA 00641 (LINC00641) in BC remain unidentified. This study shows that LINC00641 expression level was decreased in BC tissues. LINC00641 expression level was negatively related to tumor size, lymph-node metastasis, as well as clinical stage. LINC00641 overexpression inhibited cell proliferation, migration, and invasion but stimulated apoptosis in BC cells. LINC00641 overexpression also remarkably reduced BC growth and metastasis in vivo. LINC00641 acts as a competitive endogenous RNA to sponge miR-194-5p. miR-194-5p level was higher in BC tissues and cells compared with normal-adjacent tissues and normal breast epithelial cell. miR-194-5p expression was negatively correlated with LINC00641 expression in BC tissues. miR-194-5p overexpression reversed the effects of LINC00641 on cell proliferation, cycle, apoptosis, migration, as well as invasion. In conclusion, LINC00641 inhibits BC cell proliferation, migration, as well as invasion by sponging miR-194-5p.     

Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression

BackgroundIt has been known for decades that circRNAs are deregulated in cancer. Here, we characterized the role and underlying mechanism of circ_0088212 in osteosarcoma.MethodsThe expression levels of circ_0088212, miR-520 h, and APOA1 were determined by RT-qPCR. RNase R digestion was performed to verify the circular structure of circ_0088212. CCK8 and transwell invasion assays were conducted to examine the in vitro malignancy of osteosarcoma. Caspase-3 activity was also measured.An in vivo model of osteosarcoma was constructed to examine the in vivo effect of circ_0088212 on osteosarcoma. Luciferase reporter, RNA RIP, and RNA pull-down assays were performed to verify the interaction between miR-520 h and APOA1 or circ_0088212.ResultsCirc_0088212 and APOA1 were expressed at low levels in osteosarcoma tissues and cells, while miR-520 h was highly expressed. Overexpression of circ_0088212 was found to inhibit the in vitro and in vivo growth of osteosarcoma. Mechanistically, miR-520 h was the target of circ_0088212 and APOA1 was the target of miR-520 h. Circ_0088212 downregulated miR-520 h expression, while miR-520 h overexpression abolished the inhibitory effect of circ_0088212 on osteosarcoma cell proliferation and migration. Furthermore, miR-520 h overexpression led to reduced APOA1 expression, while APOA1 overexpression counteracted the oncogenic effect of miR-520 h in osteosarcoma cells.ConclusionOur findings demonstrated that circ_0088212 might exert a tumor-suppressive activity in osteosarcoma by sponging and sequestering miR-520 h away from APOA1. This suggests that the circ_0088212/miR-520 h/APOA1 axis may be a promising therapeutic target for osteosarcoma intervention.