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Numerous studies have indicated enrichment of circular RNA (circRNA) in the brain takes on a momentous role in cerebral ischemia‐reperfusion (CIR) injury. A recent study discovered a novel circCRIM1, was highly expressed in the middle cerebral artery occlusion‐reperfusion (MCAO/R) model. Nevertheless, its specific biological function remained unknown. The study was to explore circCRIM1 in CIR‐induced neuronal apoptosis. As measured, circCRIM1 and TXNIP were up‐regulated, while miR‐141‐3p was down‐regulated in MCAO/R mouse model and OGD/R SH‐SY5Y cells. Depleting circCRIM1 reduced the number of apoptotic neurons in MCAO/R rats, increased the number of Nissl bodies, prevented reactive oxygen species production and oxidative stress imbalance in brain tissues, repressed cleaved caspase‐3, Bax, and Cyto C protein levels and increased Bcl‐2 levels. Overexpression of circCRIM1 further repressed neuronal activity and accelerated apoptosis in OGD/R model, disrupted redox balance. Depleting circCRIM1 had the opposite effect in OGD/R model. Knocking down miR‐141‐3p or TXNIP weakened the effects of knocking down circCRIM1 or overexpressing circCRIM1, separately. Mechanistically, circCRIM1 exerted an active role in CIR injury via miR‐141‐3p to mediate TXNIP. All in all, the circCRIM1/miR‐141‐3p/TXNIP axis might be a latent therapeutic target for CIR injury. [ABSTRACT FROM AUTHOR]

Background: Preeclampsia (PE) is a severe complication that occurs during pregnancy and a main cause of perinatal mortality of mothers as well as infants, which is characterized by abnormal placental trophoblast. Previous study reported that aberrant circular RNA (circRNA) was involved in the pathogenesis and progression of PE. Herein, we aimed to investigate the role of circCRIM1 and explore the mechanism of circCRIM1 in PE. Methods: The quantitative real‐time PCR (qRT‐PCR) was conducted to determine the relative expression of circCRIM1, miR‐942‐5p, and IL1RAP in tissues and cells. Cell proliferation viability was assessed by both MTT and EdU assays. Cell cycle distribution was analyzed using flow cytometry. Transwell assay was performed to test the cell migration and invasion. The protein levels of CyclinD1, MMP9, MMP2, and IL1RAP were measured by western blot. The putative binding sites between miR‐942‐5p and circCRIM1 or IL1RAP 3′UTR were verified by dual‐luciferase reporter gene assay. Rescue experiment was performed to confirm that miR‐942‐5p/IL1RAP axis was functional target of circCRIM1 in trophoblast cells. Results: CircCRIM1 was upregulated in placenta tissues of PE and its expression was inversely related to infant weight. Overexpression of circCRIM1 suppressed proliferation, migration, and invasion and reduced the protein levels of CyclinD1, MMP9, MMP2 of trophoblast cells, whereas its knockdown exerted the opposite effect. CircCRIM1 could interact with miR‐942‐5p, and introduction of miR‐942‐5p partially abated the inhibitory effect of circCRIM1 on trophoblast cell behaviors. IL1RAP was directly targeted and negatively regulated by miR‐942‐5p. miR‐942‐5p played its regulatory role on cell proliferation, migration, and invasion of trophoblast by IL1RAP. Further analysis showed that circCRIM1 modulated IL1RAP expression via sponging miR‐942‐5p. Conclusion: The results of the present study demonstrated that circCRIM1 inhibited the proliferation, migration, and invasion of trophoblast cells through sponging miR‐942‐5p and up‐regulating IL1RAP, providing a possible new mechanism of PE. [ABSTRACT FROM AUTHOR]

Liu J, Feng G, Li Z, Li R, Xia P. Cancer Manag Res. 2020;12:10199–10210. We, the Editors and Publisher of Cancer Management and Research, have retracted the following article. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors did not respond to our queries, nor did they provide original data for their study. As verifying the validity of the published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Abstract Background Nasopharyngeal carcinoma (NPC) is a rare malignancy with multiple risk factors (Epstein–Barr virus, etc.) that seriously threatens the health of people. CircRNAs are known to regulate the tumorigenesis of malignant tumours, including NPC. Moreover, circCRIM1 expression is reported to be upregulated in NPC. Nevertheless, the impact of circCRIM1 on NPC progression is not clear. Methods An MTT assay was performed to assess cell viability. In addition, cell invasion and migration were assessed by the transwell assay. Dual luciferase assays were performed to assess the association among circCRIM1, miR-34c-5p and FOSL1. Moreover, RT-qPCR was applied to assess mRNA levels, and protein levels were determined by Western blot. Results CircCRIM1 and FOSL1 were upregulated in NPC cells, while miR-34c-5p was downregulated. Knockdown of circCRIM1 significantly decreased the invasion, viability and migration of NPC cells. The miR-34c-5p inhibitor notably promoted the malignant behaviour of NPC cells, while miR-34c-5p mimics exerted the opposite effect. Moreover, circCRIM1 could bind with miR-34c-5p, and FOSL1 was identified to be downstream of miR-34c-5p. Furthermore, circCRIM1 downregulation notably inhibited the proliferation and invasion of NPC cells, while this phenomenon was significantly reversed by FOSL1 overexpression. Conclusion Silencing circCRIM1 inhibited the tumorigenesis of NPC. Thus, circCRIM1 might be a novel target for NPC.

Abstract Background Ovarian cancer is the leading cause of death in patients with gynecologic cancer, and circular RNAs (circRNAs) are involved in cancer progression. However, there are limited studies on the roles of circRNAs in ovarian cancer. Methods We designed divergent and convergent primers, used sanger sequencing and RNase R digestion to verify the source of circCRIM1. We detected the expression of circCRIM1 and its parental gene cysteine rich transmembrane BMP regulator 1 (CRIM1) in ovarian cancer and normal ovarian samples via qRT-PCR. MTT viability assay, apoptosis assay, wound healing assay and invasion assay were used to investigate the function of circCRIM1 and CRIM1 in ovarian cancer cell lines OVCAR3 and CAOV3. Mice xenografts experiment was performed. Bioinformatics predicted the microRNAs that bond with circCRIM1 and CRIM1, and dual luciferase reporter system confirmed it. Rescue experiments of microRNAs mimics transfection on the basis of circCRIM1 over-expression were carried out to uncover the mechanism by which circCRIM1 played cancer-promoting roles in ovarian cancer. Results CircCRIM1 was derived from CRIM1 by back-splicing. CircCRIM1 and CRIM1 had higher expression in ovarian cancer than in normal ovarian tissues, and both of them promoted ovarian cancer progression in vitro. In vivo circCRIM1 promoted the growth of tumors. CircCRIM1 and CRIM1 had a positive correlation relationship in the same cohort of ovarian cancer tissues. Bioinformatics predicted and dual luciferase assay confirmed circCRIM1 and CRIM1 bond with miR-145-5p, and circCRIM1 bond with miR-383-5p additionally. CircCRIM1 positively affected the expression of CRIM1. After circCRIM1 was over-expressed, miR-145-5p mimics transfection reversed the expression of CRIM1. Western blot discovered circCRIM1 positively affected the expression of zinc finger E-box binding homeobox 2 (ZEB2). Rescue experiments found miR-383-5p mimics reversed ZEB2 expression and the cancer-promoting effects of circCRIM1. Conclusions CircCRIM1 bond with miR-145-5p to work as competing endogenous RNA (ceRNA) of CRIM1, and circCRIM1 bond with miR-383-5p to improve the expression of ZEB2 in ovarian cancer. CircCRIM1 and CRIM1 promoted the ovarian cancer progression and supplied a novel insight into the researches of ovarian cancer.

Background: Nasopharyngeal carcinoma (NPC) is a rare malignancy with multiple risk factors (Epstein–Barr virus, etc.) that seriously threatens the health of people. CircRNAs are known to regulate the tumorigenesis of malignant tumours, including NPC. Moreover, circCRIM1 expression is reported to be upregulated in NPC. Nevertheless, the impact of circCRIM1 on NPC progression is not clear. Methods: An MTT assay was performed to assess cell viability. In addition, cell invasion and migration were assessed by the transwell assay. Dual luciferase assays were performed to assess the association among circCRIM1, miR-34c-5p and FOSL1. Moreover, RT-qPCR was applied to assess mRNA levels, and protein levels were determined by Western blot. Results: CircCRIM1 and FOSL1 were upregulated in NPC cells, while miR-34c-5p was downregulated. Knockdown of circCRIM1 significantly decreased the invasion, viability and migration of NPC cells. The miR-34c-5p inhibitor notably promoted the malignant behaviour of NPC cells, while miR-34c-5p mimics exerted the opposite effect. Moreover, circCRIM1 could bind with miR-34c-5p, and FOSL1 was identified to be downstream of miR-34c-5p. Furthermore, circCRIM1 downregulation notably inhibited the proliferation and invasion of NPC cells, while this phenomenon was significantly reversed by FOSL1 overexpression. Conclusion: Silencing circCRIM1 inhibited the tumorigenesis of NPC. Thus, circCRIM1 might be a novel target for NPC. [ABSTRACT FROM AUTHOR]

Jun Liu,1 Guang Feng,2 Zhengwei Li,3 Rui Li,1 Peng Xia1 1Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, Jilin 130000, People’s Republic of China; 2The Fourth Medical Center of PLA General Hospital, Beijing 100048, People’s Republic of China; 3Department of Orthopaedics, The Second Hospital of Jilin University, Jilin 130000, People’s Republic of ChinaCorrespondence: Peng XiaDepartment of Orthopaedics, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Nanguan District, Changchun 130000, Jilin Province, People’s Republic of China, Tel +86-043181136193Email puonmx@163.comBackground: Circular RNAs (circRNAs) serve for a genre of considerable modulatory molecules that have been largely researched in human cancers. However, the contribution of circRNA cysteine-rich transmembrane bone morphogenetic protein regulator 1 (circCRIM1) to osteosarcoma (OS) is completely unclear.Methods: All the RNA levels were examined via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular proliferation and migration/invasion were, respectively, analyzed using 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay and transwell assay. The determination of all protein expression was administrated by Western blot. Dual-luciferase reporter assay was used for proving the target combination. The exploration of circCRIM1 in vivo was performed by xenograft assay.Results: In OS tissues and cells, circCRIM1 was differentially up-regulated. Functionally, cell proliferation, migration and invasion were suppressed while autophagy was promoted after circCRIM1 was down-regulated in OS cells. Mechanistically, mircoRNA-432-5p (miR-432-5p) was a miRNA target of circCRIM1 and the inhibitory effect of circCRIM1 knockdown on OS progression was achieved by targeting miR-432-5p. Moreover, histone deacetylase 4 (HDAC4) was a downstream gene of miR-432-5p and circCRIM1 targeted miR-432-5p to up-regulate HDAC4 level. MiR-432-5p inhibited proliferation, migration, and invasion but enhanced autophagy of OS cells through down-regulating HDAC4. In vivo, knockdown of circCRIM1 decreased OS growth via acting on the miR-432-5p/HDAC4 axis.Conclusion: Our findings elucidated the oncogenic function of circCRIM1 in OS via the regulation of the miR-432-5p/HDAC4 axis, affording a novel view about how circRNA participated in OS development.Keywords: circCRIM1, osteosarcoma, miR-432-5p, HDAC4

Mounting evidence has demonstrated that circular RNAs have an important function in tumorigenesis and cancer evolvement. CircCRIM1 has been shown to be a poor prognostic element in multiple human malignancies. However, the clinical significance and mechanism of circCRIM1 in hepatocellular carcinoma (HCC) is still unclear. The present study confirmed the expression level of circCRIM1 using quantitative real-time PCR. In addition, circCRIM1 siRNA and overexpression vectors were used for transfection into LM3 or Huh7 cells to down- or up-regulate the expression of circCRIM1. In vitro and in vivo experiments were performed to explore the function of circCRIM1 in HCC. RNA pull-down, RNA immunoprecipitation, fluorescent in situ hybridization, and luciferase reporter assays were conducted to confirm the relationship between miR-378a-3p and circCRIM1 or S-phase kinase-associated protein 2 (SKP2) in HCC. Then, circCRIM1 was up-regulated in HCC and its expression level was significantly associated with poor prognosis and clinicopathologic characteristics. CircCRIM1 enhanced the proliferation and angiogenesis of HCC cells in vitro and promoted xenograft growth in vivo. Moreover, circCRIM1 upregulated the expression of SKP2 by functioning as a sponge for miR-378a-3p. These findings suggest that circCRIM1 boosts the HCC progression via the miR-378-3p/SKP2 axis and may act as a crucial epigenetic therapeutic molecule target in HCC.

Background: Ovarian cancer is the leading cause of death in patients with gynecologic cancer, and circular RNAs (circRNAs) are involved in cancer progression. However, there are limited studies on the roles of circRNAs in ovarian cancer. Methods: We designed divergent and convergent primers, used sanger sequencing and RNase R digestion to verify the source of circCRIM1. We detected the expression of circCRIM1 and its parental gene cysteine rich transmembrane BMP regulator 1 (CRIM1) in ovarian cancer and normal ovarian samples via qRT-PCR. MTT viability assay, apoptosis assay, wound healing assay and invasion assay were used to investigate the function of circCRIM1 and CRIM1 in ovarian cancer cell lines OVCAR3 and CAOV3. Mice xenografts experiment was performed. Bioinformatics predicted the microRNAs that bond with circCRIM1 and CRIM1, and dual luciferase reporter system confirmed it. Rescue experiments of microRNAs mimics transfection on the basis of circCRIM1 over-expression were carried out to uncover the mechanism by which circCRIM1 played cancer-promoting roles in ovarian cancer. Results: CircCRIM1 was derived from CRIM1 by back-splicing. CircCRIM1 and CRIM1 had higher expression in ovarian cancer than in normal ovarian tissues, and both of them promoted ovarian cancer progression in vitro. In vivo circCRIM1 promoted the growth of tumors. CircCRIM1 and CRIM1 had a positive correlation relationship in the same cohort of ovarian cancer tissues. Bioinformatics predicted and dual luciferase assay confirmed circCRIM1 and CRIM1 bond with miR-145-5p, and circCRIM1 bond with miR-383-5p additionally. CircCRIM1 positively affected the expression of CRIM1. After circCRIM1 was over-expressed, miR-145-5p mimics transfection reversed the expression of CRIM1. Western blot discovered circCRIM1 positively affected the expression of zinc finger E-box binding homeobox 2 (ZEB2). Rescue experiments found miR-383-5p mimics reversed ZEB2 expression and the cancer-promoting effects of circCRIM1. Conclusions: CircCRIM1 bond with miR-145-5p to work as competing endogenous RNA (ceRNA) of CRIM1, and circCRIM1 bond with miR-383-5p to improve the expression of ZEB2 in ovarian cancer. CircCRIM1 and CRIM1 promoted the ovarian cancer progression and supplied a novel insight into the researches of ovarian cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity. Results We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients. Conclusions Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients.

OBJECTIVE: The present studies indicate that circRNAs play pivotal roles in human cancers. Lung adenocarcinoma (LUAC), one of lung cancer types, has high metastasis rate. Herein, we focused our study on the function and mechanism of circular RNA circCRIM1 in LUAC development. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was performed to detect the levels of circCRIM1, miR-125b-5p, and BTG anti-proliferation factor 2 (BTG2). Transwell assay was carried out to assess cell migration and invasion. The protein levels of BTG2, EMT markers, and HK2 were measured by Western blot. Glycolysis was analyzed through determining glucose consumption and lactate production. Furthermore, the targets of circCRIM1 and miR-125b-5p were predicted and verified by starBase and the dual-luciferase reporter assay, respectively. Also, whether circ-CRIM1 affecting tumor growth in vivo was explored using mouse xenograft assay. RESULTS: CircCRIM1 and BTG2 were downregulated, and miR-125b-5p was upregulated in LUAC tissues/cells. CircCRIM1 upregulation inhibited LUAC cell migration, invasion, epithelial-mesenchymal transition (EMT), glycolysis, and tumor growth. Moreover, circCRIM1 regulated LUAC cell development through targeting miR-125b-5p. MiR-125b-5p affected LUAC cell growth via binding to BTG2. Also, circCRIM1 promoted BTG2 expression by inhibiting miR-125b-5p expression in LUAC cells. CONCLUSIONS: CircCRIM1 was lowly expressed in LUAC. Moreover, circCRIM1 functioned as a sponge of miR-125b-5p to improve BTG2 expression, thereby suppressing LUAC development. Our finding indicated that circCRIM1 could be considered as a biomarker and target for the diagnosis and therapy of LUAC patients. [ABSTRACT FROM AUTHOR]

Background: Circular RNAs (circRNAs), a new type of noncoding RNA (ncRNA), have been identified as significant gene expression regulators and are involved in cancer progression. However, the roles of circRNAs in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods: Here, the expression profile of circRNAs in a pair of NPC cell lines with different metastatic abilities (S18 and S26 cells) was analyzed by RNA-sequencing. Quantitative reverse transcription PCR was used to detect the expression level of circCRIM1 in NPC cells and tissues. Then, function experiments in vitro and in vivo were performed to evaluate the effects of circCRIM1 on NPC metastasis and EMT. Mechanistically, RNA immunoprecipitation, luciferase reporter assay, pull-down assay with biotinylated miRNA, fluorescent in situ hybridization were performed to confirm the interaction between circCRIM1 and miR-422a in NPC. The clinical value of circCRIM1 was evaluated in NPC metastasis and chemosensitivity. Results: We identified that circCRIM1 was upregulated in highly metastatic NPC cells. CircCRIM1 was also overexpressed in NPC tissues with distant metastasis, and its overexpression promoted NPC cell metastasis and EMT. Mechanistically, circCRIM1 competitively bound to miR-422a and prevented the suppressive effects of miR-422a on its target gene FOXQ1, which finally led to NPC metastasis, EMT and docetaxel chemoresistance. Furthermore, high circCRIM1 expression was associated with unfavorable survival in NPC patients. We established a prognostic model based on circCRIM1 expression and N stage that effectively predicted the risk of distant metastasis and treatment response to docetaxel-containing induction chemotherapy in NPC patients. Conclusions: Our findings reveal the critical role of circCRIM1 specifically in promoting NPC metastasis and chemoresistance via a ceRNA mechanism and provide an exploitable biomarker and therapeutic target for prognosis and treatment resistance in NPC patients. [ABSTRACT FROM AUTHOR]

In recent years, circular RNAs (circRNAs) have been revealed to have important roles in carcinogenesis. Metastasis is the leading cause of lung adenocarcinoma (LUAC) death. However, the contributions of circRNA to the metastasis of LUAC remain largely unknown. Based on circBase data and our biobank tissues, we identified circCRIM1 (a circRNA derived from exons 2, 3 and 4 of the CRIM1 gene, hsa_circ_0002346) as having a significantly decreased expression in LUAC samples compared with matched normal control samples. Both in vivo and in vitro experiments revealed that circCRIM1 suppresses the invasion and metastasis of LUAC. In vitro precipitation of circRNAs, luciferase reporter assay, and biotin‐coupled microRNA capture were carried out to investigate the Ago2‐dependent interaction of circCRIM1 and microRNA (miR)‐93/miR‐182. Mechanistically, we found that circCRIM1 could promote the expression of leukemia inhibitory factor receptor, a well‐known tumor suppressor, by sponging miR‐93 and miR‐182. In the clinical and pathological analyses, the downregulation of circCRIM1 in LUAC was significantly correlated with lymphatic metastasis and TNM stage, which served as an independent risk factor for the overall survival of patients with LUAC. Our study showed that circCRIM1 inhibits the invasion and metastasis of lung adenocarcinoma cancer cells, which makes it a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) has an escalating morbidity and a dismal prognosis. Obesity has been reported to be strongly linked to adverse TNBC outcomes. Exosomes (Exos) transport RNA and proteins between cells and serve as intermediaries for cell-to-cell communication. Accumulated evidence suggests that adipose-secreted circular RNAs (circRNAs) can modulate protein glycosylation in TNBC to facilitate tumor cell outgrowth. Herein, exo-circCRIM1 expression was found to be elevated in TNBC patients with a high body fat percentage. Functional experiments demonstrated that by inhibiting miR-503–5p, exo-circCRIM1 enhanced TNBC evolution and metastasis while activating glycosylation hydrolase OGA. Furthermore, OGA negatively regulates FBP1 by decreasing its protein stability. Moreover, the levels of OGA and FBP1 were positively related to the infiltration level of some immune cells in TNBC. These findings indicate that exo-cirCRIM1 secreted by adipocytes contributes to TNBC progression by inhibiting miR-503–5p and activating the OGA/FBP1 signaling pathway. The findings reveal a novel intercellular signaling pathway mediated by adipose-derived exosomes and suggest that treatment targeting the secreted exosome-circCRIM1 may reverse TNBC progression. • Exo-circCRIM1 expression was found to be elevated in TNBC patients with a high body fat percentage. • Exo-circCRIM1 facilitates TNBC progression and metastasis by activating the glycosylated hydrolase OGA as well as the expression of FBP1. • Exo-cirCRIM1 secreted by adipocytes contributes to TNBC progression by inhibiting miR-503–5p and activating the OGA/FBP1 signaling pathway. [ABSTRACT FROM AUTHOR]

CircCRIM1 (hsa_circ_0002346) is a circular RNA derived from gene CRIM1 (the cysteine rich transmembrane BMP regulator 1 circRNAs) by back-splicing. Recent studies have suggested the diverse function of CircCRIM1 in the tumorigenesis of multiple malignancies, including osteosarcoma (OS). Here, we investigated the role and mechanism of circCRIM1 during OS progression. Differentially expressed circRNAs (including circCRIM1) in OS and human osteoblast (hFOB1.19) cell lines were selected by searching the circRNA expression microarray dataset of GSE96964. The expression levels of circCRIM1 and its sponging miRNAs and target genes were examined by RT-qPCR. The effects of circCRIM1 on the proliferation, migration, and invasion of OS cells were investigated by in vitro gain of function experiments. The in vivo function of circCRIM1 on OS was evaluated by measuring the subcutaneous and in situ tumor growth in nude mice. In addition, dual-luciferase reporter assay and in situ hybridization (FISH) were performed to explore the underlying mechanisms of circCRIM1 and its sponging miRNAs and target genes in OS. CircCRIM1 is downregulated in human OS cell lines and predominantly presents in the cytoplasm as demonstrated by RT-qPCR and FISH assays. Overexpression of circCRIM1 suppressed the migration, invasion, proliferation of OS cells in vitro and OS tumor growth in vivo . Mechanistically, we identified miR146a-5p as a sponge miRNA of circCRIM1 through bioinformatic prediction and confirmed their interaction and colocalization via reporter gene assay and FISH analysis. This interaction leads to increase expression of the downstream target gene NUMB, which will cause inhibition of the Notch signal pathway. We further demonstrated that miR146a-5p overexpression could reverse the antitumor effect induced by circCRIM1 in OS cells. Our results support that circCRIM1 acts as a tumor suppressor in OS by sponging miR146a-5p and its downstream target NUMB., Competing Interests: None., (AJCR Copyright © 2023.)