scholarly journals Circular RNA circPVT1 Contributes to Doxorubicin (DXR) Resistance of Osteosarcoma Cells by Regulating TRIAP1 via miR-137

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Dan Li ◽  
Yan Huang ◽  
Gang Wang
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Tumor Model ◽  
B Cell Lymphoma ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteosarcoma Cells ◽  
Western Blot Assay

Background. Chemoresistance is a major obstacle to the treatment of osteosarcoma patients. Circular RNA (circRNA) circPVT1 has been reported to be related to the doxorubicin (DXR) resistance in osteosarcoma. This study is designed to explore the role and mechanism of circPVT1 in the DXR resistance of osteosarcoma. Methods. circPVT1, microRNA-137 (miR-137), and TP53-regulated inhibitor of apoptosis 1 (TRIAP1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The protein levels of ATP-binding cassette, subfamily C, member 1 (ABCC1), multidrug resistance-associated protein 1 (MRP-1), cleaved- (c-) caspase-3, B-cell lymphoma-2 (Bcl-2), and TRIAP1 were examined by a western blot assay. Cell viability, proliferation, and apoptosis were detected by cell counting kit-8 (CCK-8), colony formation, and flow cytometry assays, severally. The binding relationship between miR-137 and circPVT1 or TRIAP1 was predicted by starbase 3.0 and then verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. The biological role of circPVT1 in osteosarcoma tumor growth and drug resistance was examined by the xenograft tumor model in vivo. Results. circPVT1 and TRIAP1 were highly expressed, and miR-137 was decreased in DXR-resistant osteosarcoma tissues and cells. Moreover, circPVT1 knockdown could boost DXR sensitivity by inhibiting DXR-caused proliferation and DXR-induced apoptosis in DXR-resistant osteosarcoma cells in vitro. The mechanical analysis discovered that circPVT1 acted as a sponge of miR-137 to regulate TRIAP1 expression. circPVT1 silencing increased the drug sensitivity of osteosarcoma in vivo. Conclusion. circPVT1 boosted DXR resistance of osteosarcoma cells partly by regulating the miR-137/TRIAP1 axis, hinting a promising therapeutic target for the osteosarcoma treatment.

scholarly journals CircSAMD4A contributes to cell doxorubicin resistance in osteosarcoma by regulating the miR-218-5p/KLF8 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 848-859
Author(s):  
Wei Wei ◽  
Liefeng Ji ◽  
Wanli Duan ◽  
Jiang Zhu
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Circular Rna ◽  
Resistant Cell ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Osteosarcoma Cells

AbstractCircular RNA sterile alpha motif domain containing 4A (circSAMD4A) was found to be differentially expressed in osteosarcoma and contributed to the tumorigenesis of osteosarcoma. However, the role of circSAMD4A in doxorubicin (DXR) resistance of osteosarcoma is yet to be elucidated. Levels of circSAMD4A, microRNA (miR)-218-5p and Krüppel-like factor 8 (KLF8) were detected using quantitative reverse transcription-polymerase chain reaction. Western blot was applied to detect the protein levels of KLF8, cyclin D1 and p21. Cell viability, cell cycle, migration and invasion were analyzed using Cell Counting Kit-8 assay, flow cytometry and transwell assay, respectively. The interaction between miR-218-5p and circSAMD4A or KLF8 was verified using dual-luciferase reporter assay or RNA immunoprecipitation assay. In vivo experiments were performed using murine xenograft models. CircSAMD4A and KLF8 were elevated in osteosarcoma, and knockdown of circSAMD4A or KLF8 sensitized osteosarcoma cells to DXR by mediating resistant cell viability, migration and invasion inhibition, and cell cycle arrest in vitro. miR-218-5p was decreased in osteosarcoma, and miR-218-5p inhibition enhanced DXR resistance. Besides, miR-218-5p was found to bind to circSAMD4A or KLF8, and subsequent rescue experiments indicated that miR-218-5p inhibition reversed the inhibitory effects of circSAMD4A silencing on DXR resistance, and silencing miR-218-5p enhanced DXR resistance by targeting KLF8 in osteosarcoma cells. Moreover, circSAMD4A could indirectly regulate KLF8 via miR-218-5p. Additionally, circSAMD4A knockdown enhanced the cytotoxicity of DXR in osteosarcoma in vivo via regulating miR-218-5p and KLF8. In all, circSAMD4A enhanced cell DXR resistance in osteosarcoma by regulating the miR-218-5p/KLF8 axis, suggesting a novel therapeutic target for therapy-resistant osteosarcoma.

scholarly journals Circular RNA circHECTD1 prevents Diosbulbin-B-sensitivity via miR-137/PBX3 axis in gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yizhuo Lu ◽  
Long Li ◽  
Lianghui Li ◽  
Guoyang Wu ◽  
Guoyan Liu
Keyword(s):  
Gastric Cancer ◽  
Expression Profiles ◽  
Tumor Model ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Diagnosis And Prognosis ◽  
The Impact

Abstract Backgrounds Gastric cancer (GC) is general disease in human digestive system with malignancy. Emerging findings indicated that hsa_circ_0031452 (circHECTD1) was strictly associated with carcinogenesis. Nevertheless, the role of circHECTD1 in drug-resistance still needed to be explained. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to examine the expression profiles of circHECTD1, microRNA (miR)-137, and pre-leukemia transcription factor 3 (PBX3). The function of circHECTD1 in tumorigenesis was evaluated via xenograft tumor model. The IC50 of Diosbulbin-B (DB) was detected using Cell Counting Kit-8 (CCK8). Cell-cycle and apoptosis were reckoned by flow cytometry. Besides, western blot was administrated to reckon the levels of PBX3 and cell apoptotic indicators. Moreover, the interrelation between miR-137 and circHECTD1 or PBX3 was expounded by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull down assays. Results We uncovered that circHECTD1 was ectopically up-regulated in GC tissues and cells. CircHECTD1 deficiency sensitized DB-treatment in DB-evoked AGS and HGC-27 cells. In vivo assay, circHECTD1 silencing led to the tumor reduction. Also, circHECTD1 served as miR-137 sponge in a sequence-complementary manner. Furthermore, transfection of miR-137 inhibitor markedly eliminated circHECTD1 absence-mediated promotion of DB-sensitivity in GC cells. Moreover, PBX3, a target of miR-137, play a DB-resistant role in GC cells. Fascinatingly, the deletion of PBX3 reversed the impact of miR-137 repression and circHECTD1 knockdown on DB-sensitivity in vitro. Conclusions CircHECTD1 served as an oncogene by a novel miR-137/PBX3 axis, which might supply an underlying biomarker for the diagnosis and prognosis of GC management.

scholarly journals LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

2020 ◽  
Vol 15 (1) ◽  
pp. 871-883
Author(s):  
Jinshan Zhang ◽  
Dan Rao ◽  
Haibo Ma ◽  
Defeng Kong ◽  
Xiaoming Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Noncoding Rna ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

scholarly journals Circular RNA hsa_circ_0013958 Functions as an Oncogenic Gene Through Modulating miR-532-3p/WEE1 Axis in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Ma ◽  
Yue Ma ◽  
Yongjun Du ◽  
Zhongheng Wei ◽  
Jianchu Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Polymerase Chain ◽  
Oncogenic Gene ◽  
Proliferation And Invasion

Backgroundcirc0013958 was identified as a biomarker, which can be used for the diagnosis and screening of lung cancer. However, the role of circ0013958 in hepatocellular carcinoma (HCC) remains unclear.MethodsIn our study, quantitative real-time polymerase chain reaction was performed to determine the levels of circ0013958 in HCC tissues and cell lines. EdU, CCK-8, transwell, flow cytometry and tumorigenesis assays were applied to assess the functions of circ0013958 in HCC in vitro and in vivo. Western blot assay was to detect the expression of WEE1. Luciferase reporter assay, bioinformatics analysis and rescue experiments were used to examine the interaction among circ0013958, miR-532-3p and WEE1.ResultsIt revealed that circ0013958 was significantly up-regulated in HCC, which was positively correlated with poor prognosis of HCC patients. Circ0013958 promoted HCC cell proliferation and invasion, inhibited cell apoptosis in vitro, and promoted tumorigenesis in vivo. Circ0013958 acted as a miR-532-3p sponge to regulate WEE1 expression, thus promoting the progression of HCC.ConclusionsCirc0013958 promotes HCC progression through miR-532-3p/WEE1 axis. Circ0013958 may serve as a potential diagnostic biomarker and therapeutic target of HCC.

scholarly journals Circular RNA circ-PVT1 contributes to paclitaxel resistance of gastric cancer cells through the regulation of ZEB1 expression by sponging miR-124-3p

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Yan-yan Liu ◽  
Li-ying Zhang ◽  
Wen-zhen Du
Keyword(s):  
Gastric Cancer ◽  
Tumor Model ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Western Blot Assay ◽  
Protein Levels ◽  
Zeb1 Expression ◽  
Resistant Cells

Abstract Gastric cancer (GC) is the fifth most commonly diagnosed malignancy. Paclitaxel (PTX) is an effective first-line chemotherapy drug in GC treatment, but the resistance of PTX attenuates the therapeutic effect. Circular RNA circ-PVT1 can exert the oncogenic effect in GC. But the function of circ-PVT1 involved in PTX resistance of GC is still unknown. In the present study, the expression levels of circ-PVT1, miR-124-3p and ZEB1 in PTX-resistant GC tissues and cells were detected by quantitative real-time polymerase chain reaction (RT-qPCR). PTX resistance in PTX-resistant cells was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The protein levels of Zinc finger E-box binding homeobox 1 (ZEB1), P-glycoprotein (P-gp) and glutathione S-transferase (GST-π) were detected by Western blot assay. Cell apoptosis and invasion were measured in PTX-resistant cells by flow cytometry and transwell invasion assays, severally. The interaction between miR-124-3p and circ-PVT1 or ZEB1 was predicted by starBase software, and then verified by the dual-luciferase reporter assay. The role of circ-PVT1 in PTX resistance of GC in vivo was measured by xenograft tumor model. Our results showed that circ-PVT1 expression was up-regulated in PTX-resistant GC tissues and cells. Circ-PVT1 down-regulation enhanced PTX sensitivity in PTX-resistant GC cells by negatively regulating miR-124-3p. ZEB1 served as a direct target of miR-124-3p. Circ-PVT1 enhanced ZEB1 expression by sponging miR-124-3p. Circ-PVT1 knockdown increased PTX sensitivity of GC in vivo. Taken together, our studies disclosed that circ-PVT1 facilitated PTX resistance by up-regulating ZEB1 mediated via miR-124-3p, suggesting an underlying therapeutic strategy for GC.

scholarly journals Long noncoding RNA AFAP1-AS1 promotes tumor progression and invasion by regulating the miR-2110/Sp1 axis in triple-negative breast cancer

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaohui Zhang ◽  
Fangyuan Li ◽  
Yidong Zhou ◽  
Feng Mao ◽  
Yan Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Noncoding Rna ◽  
Triple Negative ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion

AbstractLong noncoding ribonucleic acids (LncRNAs) have been found to be involved in the proliferation, apoptosis, invasion, migration, and other pathological processes of triple-negative breast cancer (TNBC). Expression of the lncRNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) has been found to be significantly higher in TNBC than in other subtypes or in normal tissue samples, but the specific mechanism by which AFAP1-AS1 affects the occurrence and development of TNBC is yet to be revealed. In this study, we used Cell Counting Kit-8 (CCK-8), colony formation, wound healing migration, Transwell invasion, and nude mouse xenograft assays to confirm the role of AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. In addition, we performed bioinformatics analyses, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and dual-luciferase reporter assays (dual-LRA) to confirm interaction among AFAP1-AS1, micro-RNA 2110 (miR-2110), and Sp1 transcription factor (Sp1). We found that silencing AFAP1-AS1 and Sp1 or upregulating miR-2110 suppressed the proliferation, migration, and invasion of MDA–MB-231 and MDA–MB-468 cells in vitro as well as tumor growth in vivo. Mechanistically, the dual-LRA highlighted that miR-2110 was an inhibitory target of AFAP1-AS1, and that AFAP1-AS1 functioned as a miR-2110 sponge to increase Sp1 expression. AFAP1-AS1 silencing led to a reduction in Sp1 mRNA and protein levels, which could be reversed by joint transfection with miR-2110 inhibitor. Our findings demonstrated that AFAP1-AS1 could modulate the progression of breast cancer cells and affect tumorigenesis in mice by acting as a miR-2110 sponge, resulting in regulation of Sp1 expression. Therefore, AFAP1-AS1 could play a pivotal role in the treatment of TNBC.

scholarly journals Circ_0002060 enhances doxorubicin resistance in osteosarcoma by regulating miR-198/ABCB1 axis

2020 ◽  
Author(s):  
Jun Liu ◽  
Wenshuai Zhu ◽  
Jianqin Ji
Keyword(s):  
Western Blot ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Western Blot Assay ◽  
Doxorubicin Resistance ◽  
Kaplan Meier ◽  
Rna Immunoprecipitation ◽  
Resistance To Doxorubicin

Abstract Background Osteosarcoma (OS) is a common aggressive primary sarcoma of bone. Drug resistance is a huge obstacle to chemotherapy for cancer. This study aimed to investigate the role and mechanism of circ_0002060 in OS resistance to doxorubicin (DOX). Methods The levels of circ_0002060, miR-198 and ATP binding cassette subfamily B member 1 (ABCB1) were measured by quantitative real-time polymerase chain reaction or western blot assay. Kaplan-Meier analysis was performed to determine the relationship between circ_0002060 expression and overall survival. The half inhibition concentration (IC50) of doxorubicin was calculated by Cell Counting Kit-8 (CCK-8) assay. Cell proliferation was assessed by colony formation assay. Cell apoptosis was monitored by flow cytometry. The levels of apoptosis-related proteins were measured by western blot assay. Xenograft assay was utilized to analyze the effect of circ_0002060 on DOX resistance in vivo . The interaction among circ_0002060, miR-198 and ABCB1 were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation assay or RNA pull-down assay. Results Circ_0002060 and ABCB1 were up-regulated, while miR-198 was down-regulated in OS tissues and DOX-resistant OS cells. Circ_0002060 silence reduced DOX resistance in vitro and in vivo . Moreover, circ_0002060 enhanced DOX resistance via sponging miR-198. Besides, miR-198 decreased DOX resistance by binding to ABCB1. In addition, circ_0002060 sponged miR-198 to up-regulate ABCB1 expression. Conclusion Circ_0002060 enhanced doxorubicin resistance of OS by regulating miR-198/ABCB1 axis, which provides potential therapeutic targets for OS therapy.

scholarly journals Circular RNA hsa_circ_0061395 accelerates hepatocellular carcinoma progression via regulation of the miR-877-5p/PIK3R3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanhui Yu ◽  
Lijuan Bian ◽  
Renfei Liu ◽  
Yitong Wang ◽  
Xia Xiao
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Circular Rna ◽  
Cell Counting ◽  
Regulatory Subunit ◽  
Luciferase Reporter ◽  
Hcc Cells

Abstract Background Circular RNA hsa_circ_0061395 (circ_0061395) has been reported to accelerate the advancement of hepatocellular carcinoma (HCC). However, the regulatory mechanism by which circ_0061395 modulates the progression of HCC is unclear. Methods The morphology and size of exosomes were analyzed by transmission electron microscope (TEM) and nanoparticle-tracking analysis (NTA). Protein levels were detected by western blotting. Expression levels of circ_0061395, microRNA (miR)-877-5p, and phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) mRNA were assessed by quantitative real time polymerase chain reaction (qRT-PCR). The proliferation, invasion, migration, cell cycle progression, and apoptosis were analyzed by cell counting kit-8 (CCK-8), plate clone, transwell, or flow cytometry assays. The targeting relationship between circ_0061395 or PIK3R3 and miR-877-5p was verified using the dual-luciferase reporter and/or RNA immunoprecipitation (RIP) assays. Xenograft assay was performed to confirm the biological function of circ_0061395 in HCC. Results Circ_0061395 was upregulated in HCC tissues, serum, cells, and serum-derived exosomes. Circ_0061395 silencing decreased tumor growth in vivo, and induced cell cycle arrest, apoptosis, repressed proliferation, invasion, and migration of HCC cells in vitro. MiR-877-5p was downregulated while PIK3R3 was upregulated in HCC. Circ_0061395 regulated PIK3R3 expression via competitively binding to miR-877-5p. MiR-877-5p inhibitor overturned circ_0061395 knockdown-mediated influence on malignant behaviors of HCC cells. PIK3R3 overexpression reversed the suppressive influence of miR-877-5p mimic on malignant behaviors of HCC cells. Conclusion Circ_0061395 facilitated HCC progression via regulating the miR-877-5p/PIK3R3 axis, providing a new perspective on the advancement of HCC.

scholarly journals Circular RNA circ_0081001 knockdown enhances methotrexate sensitivity in osteosarcoma cells by regulating miR-494-3p/TGM2 axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Wei Wei ◽  
Liefeng Ji ◽  
Wanli Duan ◽  
Jiang Zhu
Keyword(s):  
Cell Viability ◽  
Xenograft Model ◽  
Transglutaminase 2 ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract Background Circular RNAs (circRNAs) have been shown to participate in the chemoresistance and tumorigenesis of multiple cancers. The purpose of this research was to investigate the function of circ_0081001 in methotrexate (MTX) resistance of osteosarcoma (OS) and its potential molecular mechanism. Methods The expression of circ_0081001, cytochrome P450 family 51 subfamily A member 1 (CYP51A1), and miR-494-3p was detected by qRT-PCR. Cell viability, apoptosis, migration, and invasion were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, and transwell assay, respectively. Western blot (WB) assay was used to measure the protein levels of cleaved-caspase3 (cleaved-casp3), E-cadherin, N-cadherin, and transglutaminase-2 (TGM2). The interaction between miR-494-3p and circ_0081001 or TGM2 was predicted by bioinformatics analysis and verified using the dual-luciferase reporter assay. The mice xenograft model was established to investigate the roles of circ_0081001 in MTX resistance of OS in vivo. Results Circ_0081001 and TGM2 were upregulated, and miR-494-3p was downregulated in MTX-resistant OS tissues and cells. Moreover, circ_0081001 interference enhanced cell sensitivity to MTX through promoting apoptosis and inhibiting cell viability and metastasis in vitro. Furthermore, circ_0081001 was identified as a molecular sponge of miR-494-3p to upregulate TGM2 level. In addition, circ_0081001 knockdown inhibited MTX resistance via upregulating miR-494-3p and downregulating TGM2. Besides, circ_0081001 downregulation improved MTX sensitivity of OS in vivo. Conclusion Knockdown of circ_0081001 enhanced MTX sensitivity of OS cells through downregulating TGM2 by sponging miR-494-3p, elucidating a novel regulatory mechanism for chemoresistance of OS and providing a potential circRNA-targeted therapy for OS.

scholarly journals circ_0000467 promotes the proliferation, metastasis, and angiogenesis in colorectal cancer cells through regulating KLF12 expression by sponging miR-4766-5p

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 1415-1427
Author(s):  
Hui Chen ◽  
Chen Wu ◽  
Liang Luo ◽  
Yuan Wang ◽  
Fangxing Peng
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Reaction Cell ◽  
Western Blot Assay

Abstract Background Circular RNAs have been identified as crucial players in the initiation and progression of cancers, including colorectal cancer (CRC). The Has_circ_0000467 (circ_0000467) expression has been found to be upregulated in CRC, but its function and mechanism remain unclear. Methods The expression levels of circ_0000467, microRNA-4766-5p (miR-4766-5p), and Krueppel-like factor 12 (KLF12) were examined using reverse transcription-quantitative polymerase chain reaction. Cell proliferation was analyzed by cell counting kit-8 assay and colony formation assay. The apoptosis was measured by flow cytometry. Transwell migration and invasion assays were applied to evaluate cell metastatic ability. Angiogenesis was detected using tube formation assay. All protein expressions were quantified by western blot assay. Dual-luciferase reporter assay was used to analyze intergenic binding. Xenograft models were constructed for the experiment of circ_0000467 in vivo. Results The expression of circ_0000467 was upregulated in CRC tissues and cells. Knockdown of circ_0000467 repressed cell proliferation, metastasis, and angiogenesis, but it induced apoptosis in CRC cells. circ_0000467 targeted miR-4766-5p and inhibited the expression of miR-4766-5p. Silencing of circ_0000467 inhibited CRC progression by upregulating miR-4766-5p. miR-4766-5p suppressed the expression of target gene KLF12 and KLF12 overexpression reversed the effects of miR-4766-5p on CRC cell behaviors. circ_0000467 positively regulated the expression of KLF12 by targeting miR-4766-5p. circ_0000467 downregulation in vivo reduced CRC tumorigenesis by regulating miR-4766-5p and KLF12. Conclusion circ_0000467 acted as an oncogene in CRC through regulating KLF12 expression by sponging miR-4766-5p. Therefore, circ_0000467 can be used as an effective target in CRC diagnosis and therapy.

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