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.

     

The novel circ_0084904/miR-802/MAL2 axis promotes the development of cervical cancer

Circular RNAs (circRNAs) have been identified as critical regulators in human cancers, including cervical cancer (CC). However, the precise action of circ_0084904 in cervical carcinogenesis remains to be elucidated. The levels of circ_0084904, microRNA (miR)-802, and Mal, T cell differentiation protein 2 (MAL2) were checked by quantitative real-time PCR (qRT-PCR) or western blot. Ribonuclease R (RNase R) and subcellular localization assays were used to detect the stability and localization of circ_0084904, respectively. Cell colony formation ability was assessed by colony formation assay. Cell cycle and apoptosis were detected by flow cytometry. Cell migration and invasion abilities were gauged by transwell assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to determine the direct relationship between miR-802 and circ_0084904 or MAL2. The xenograft experiments were performed to evaluate the role of circ_0084904 in tumor growth in vivo. Circ_0084904 was markedly up-regulated in CC tissues and cell lines. Silencing endogenous circ_0084904 impeded cell colony formation, cell cycle progression, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ_0084904 targeted miR-802, and the effects of circ_0084904 silencing were mediated by miR-802. MAL2 was directly targeted and inhibited by miR-802, and MAL2 was a functional target of miR-802. Moreover, circ_0084904 modulated MAL2 expression via miR-802. Our study identified circ_0084904 as a novel oncogenic driver in CC depending on the modulation of the miR-802/MAL2 axis, establishing the notion that silencing of circ_0084904 might represent a promising targeted therapy for CC.     

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_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_0004015 silencing represses cisplatin chemoresistance and tumor progression by reducing KLF8 in a miR-198-dependent manner in non-small cell lung cancer

Circular RNA (circRNA) plays vital roles in diverse cancer progression, including non-small cell lung cancer (NSCLC). Herein, the role of circ_0004015 in regulating the sensitivity of NSCLC to cisplatin (DDP) is revealed. The RNA expression of circ_0004015, microRNA-198 (miR-198) and kruppel like factor 8 (KLF8) was detected by quantitative real-time polymerase chain reaction. Protein expression was checked by western blot. The half maximal inhibitory concentration of DDP and cell proliferation were determined by cell counting kit-8 assay. Cell colony formation ability, migration, invasion and apoptosis were investigated by colony-forming assay, transwell assay and flow cytometry analysis, respectively. The effect of circ_0004015 knockdown on DDP sensitivity in vivo was demonstrated by mouse model assay. The interactions among circ_0004015, miR-198 and KLF8 were predicted by bioinformatics methods, and identified by mechanism assays. The expression of circ_0004015 and KLF8 was apparently upregulated, while miR-198 expression was downregulated in DDP-resistant NSCLC tissues and cells compared with control groups. Additionally, circ_0004015 silencing repressed DDP resistance, cell proliferation, migration and invasion, but induced cell apoptosis in DDP-resistant NSCLC cells. Circ_0004015 knockdown promoted the effect of DDP on tumor formation in vivo. Also, miR-198 inhibitors attenuated circ_0004015 depletion-mediated action though associating with circ_0004015. MiR-198 regulated DDP sensitivity and NSCLC progression by targeting KLF8. Furthermore, circ_0004015 modulated KLF8 expression through interaction with miR-198. Circ_0004015 conferred DDP resistance and promoted NSCLC progression by miR-198/KLF8 pathway, proving a potential target for studying DDP-mediated treatment of NSCLC.     

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_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.

     

Circ_RPL23A acts as a miR-1233 sponge to suppress the progression of clear cell renal cell carcinoma by promoting ACAT2

Clear cell renal cell carcinoma (ccRCC) is a prevalent urological carcinoma with high metastatic risk. Circular RNAs (circRNAs) have been identified as effective diagnostic and therapeutic biomarkers for ccRCC. This research aims to disclose the effect and regulatory mechanism of circRNA ribosomal protein L23a (circ_RPL23A) in ccRCC. We performed quantitative real-time polymerase chain reaction (qRT-PCR) to examine circ_RPL23A, microRNA-1233 (miR-1233) and acetyl-coenzyme A acetyltransferase 2 (ACAT2). Cell cycle progression, apoptosis, cell viability, invasion and migration, which were respectively conducted by using flow cytometry, 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), transwell assays. The levels of ACAT2 protein and cell cycle proteins, proliferation-associated protein, and epithelial-mesenchymal transition (EMT) associated proteins were measured by western blot. Target relationship was analyzed via dual-luciferase reporter assay and RNA pull down assay. The animal model was used to study how circ_RPL23A affects in vivo. Circ_RPL23A was lower expressed in ccRCC tissues and cells. The elevated circ_RPL23A suppressed cell cycle progression, proliferation, migration and invasion but promoted apoptosis in ccRCC cells. MiR-1233 was a target of circ_RPL23A and direct targeted to ACAT2. Besides, circ_RPL23A exerted its anti-tumor effect by sponging miR-1233, and then relieved the inhibition effect of miR-1233 on ACAT2. Overexpression of circ_RPL23A also curbed ccRCC tumor growth in vivo. Circ_RPL23A inhibited ccRCC progression by upregulating ACAT2 expression by competitively binding miR-1233, which might provide an in-depth cognition for ccRCC pathogenesis and circ_RPL23A might be a promising biomarker in ccRCC diagnosis and treatment.

     

Circ_0079593 facilitates proliferation,metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR-516b/GRM3 axis

Many studies confirm that circular RNA (circRNA) plays an important regulatory role in the malignant progression of cancer, including melanoma. However, the role of a novel circRNA, circ_0079593, in melanoma is unclear. The expression levels of circ_0079593 and miR-516b were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was measured by cell counting kit-8 (CCK-8) assay, and cell migration and invasion were evaluated using transwell assay. Meanwhile, western blot (WB) analysis was employed to determine the levels of proliferation and metastasis-related proteins, as well as metabotropic glutamate receptor 3 (GRM3) protein. Furthermore, cell apoptosis was tested by detecting the cell apoptosis rate and Caspase-3 activity. The glucose consumption and lactate production of cells were measured to evaluate cell glucose metabolism. Moreover, dual-luciferase reporter assay and biotin-labeled RNA pull-down assay were used to confirm the interaction between miR-516b and circ_0079593 or GRM3. In addition, mice xenograft models were constructed to explore the effect of circ_0079593 on melanoma tumor growth in vivo. Our results discovered that circ_0079593 was highly expressed in melanoma, and its silencing suppressed melanoma cell proliferation, migration, invasion, glucose metabolism and promoted apoptosis. Moreover, we found that circ_0079593 could serve as a sponge of miR-516b, and miR-516b could target GRM3 in melanoma. The rescue experiments revealed that both miR-516b inhibitor and GRM3 overexpression could reverse the inhibition effect of circ_0079593 knockdown on melanoma progression. Additionally, in vivo experiments also revealed that circ_0079593 interference suppressed melanoma tumor growth. Our study concluded that circ_0079593 accelerated melanoma progression via upregulating GRM3 by sponging miR-516b, which suggested that circ_0079593 had the potential to be a new therapeutic biomarker for melanoma.

     

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.     

Circ_0021573 acts as a competing endogenous RNA to promote the malignant phenotypes of human ovarian cancer cells

Circular RNAs (circRNAs) have been reported to be implicated in the tumorigenesis and progression of ovarian cancer. Here, the study was designed to explore the activity of human circ_0021573 in ovarian cancer pathogenesis and its regulation through the competing endogenous RNA (ceRNA) crosstalk. Circ_0021573, microRNA (miR)? 936, and cullin 4B (CUL4B) were quantified by qRT-PCR and western blot. Cell proliferation ability was detected by XTT, 5-Ethynyl-2′-Deoxyuridine (EdU), and colony formation assays. Cell apoptosis, migration, and invasion were assessed by flow cytometry, wound-healing, and transwell assays, respectively. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to evaluate the direct relationship between miR-936 and circ_0021573 or CUL4B 3′UTR. Xenograft studies were applied to assess the role of circ_0021573 in tumor growth. Our data showed that circ_0021573 expression is enhanced in human ovarian cancer. Inhibition of circ_0021573 impedes cell proliferation, migration, and invasion and promotes apoptosis in vitro, as well as diminishes tumor growth in vivo. Mechanistically, circ_0021573 contains a miR-936 binding site, and miR-936 is a relevant mediator of circ_0021573 regulation. MiR-936 direct targets and inhibits CUL4B. MiR-936-mediated suppression of CUL4B hinders cell proliferation, migration, and invasion and accelerates apoptosis in vitro.. These data suggested that circ_0021573 might promote the malignant phenotypes of ovarian cancer cells by functioning as a ceRNA for miR-936 to induce CUL4B, which provided a promising target for the prevention and inhibition of ovarian cancer.     

CircRNA circ_0043533 facilitates cell growth in polycystic ovary syndrome by targeting miR-1179

Increasing evidence indicates that circular RNAs (CircRNAs) have an important role in human diseases, including polycystic ovary syndrome (PCOS). Recently, circ_0043533, a novel circRNA, was proposed to be involved in the progression of PCOS. However, its role in PCOS has not been explored. In this study, the expression levels of circ_0043533 and miR-1179 in ovarian granulosa cells (OGCs) were examined by qRT-PCR analysis. Moreover, knockdown of circ_0043533 in OGC lines COV434 and KGN, respectively, the cell viability, proliferation, apoptosis, and cycle-related markers of insulin-triggered OGCs were examined by CCK-8, EdU staining, flow cytometry, and western blot assays, respectively. The interaction between circ_0043533 and miR-1179 was examined by bioinformatics, dual-luciferase assay, and RNA immunoprecipitation. Besides, effects of the miR-1179 inhibitor on cell viability and apoptosis in OGC lines with circ_0043533 knockdown were also evaluated. OGCs and insulin-treated OGCs exhibited higher circ_0043533 levels in comparison to the IOSE80 cells. Additionally, knockdown of circ_0043533 remarkably inhibited the cell viability and proliferation and promoted the apoptosis of insulin-treated COV434 and KGN cells, respectively. Meanwhile, circ_0043533 knockdown could down-regulate the Bcl-2, CDK2, and Cyclin D1 expressions, and up-regulate the Bax levels. Furthermore, we demonstrated that circ_0043533 acted as a sponge to absorb miR-1179. Interestingly, miR-1179 inhibition remarkably attenuated the effect of circ_0043533 silence on cell proliferation and apoptosis in insulin-treated COV434 and KGN cells. Taken together, this study revealed that circ_0043533 knockdown restrained the malignant progression of PCOS via targeting miR-1179. Our data suggested that circ_0043533 would serve as a novel therapeutic target for PCOS.     

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.     

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.     

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.