Abstract
Numerous studies have suggested that the abnormal expression of circular RNAs plays an essential role in the pathological progression of numerous tumors. Nonetheless, the functions and underlying mechanisms of the circular RNA circCRIM1 in osteosarcoma (OS) are still not fully understood. In this study, 47 classes of OS tissues and adjoining normal tissues were obtained from patients. Real-time PCR was employed to measure circCRIM1 expression levels in both OS tissues and cell lines. The proliferation, migration, and invasion ability in OS cell lines were measured by MTT assays, EDU assays, transwell migration experiments, and transwell invasion assays. The results demonstrated that the expression of circCRIM1 was notably decreased both in OS tissues and cell lines. Depressed circCRIM1 expression was correlated with lymph node metastasis, advanced FIGO stage, and low overall survival of OS patients. In addition, the results indicated that circCRIM1 could decrease the migration, invasion, and growth of OS cells. Further mechanistic studies indicated that circCRIM1 served as a competing endogenous RNA (ceRNA) of miR-513, leading to decreases in the proliferation, migration, and invasion of OS cells. Taken together, our data uncovered a significant role of the circCRIM1/miR-513 pathway in the proliferation, migration, and invasion of OS cell lines and suggested that circCRIM1 may serve as a possible therapeutic target for OS treatment.
Similar content being viewed by others
References
Andersen GB, Knudsen A, Hager H, Hansen LL, Tost J (2018) miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts. Mol Oncol 12:114–131
Casali PG, Bielack S, Abecassis N, Aro HT, Bauer S, Biagini R, Bonvalot S, Boukovinas I, Bovee J, Brennan B, Brodowicz T, Broto JM, Brugieres L, Buonadonna A, De Alava E, Dei Tos AP, Del Muro XG, Dileo P, Dhooge C, Eriksson M, Fagioli F, Fedenko A, Ferraresi V, Ferrari A, Ferrari S, Frezza AM, Gaspar N, Gasperoni S, Gelderblom H, Gil T, Grignani G, Gronchi A, Haas RL, Hassan B, Hecker-Nolting S, Hohenberger P, Issels R, Joensuu H, Jones RL, Judson I, Jutte P, Kaal S, Kager L, Kasper B, Kopeckova K, Krakorova DA, Ladenstein R, Le Cesne A, Lugowska I, Merimsky O, Montemurro M, Morland B, Pantaleo MA, Piana R, Picci P, Piperno-Neumann S, Pousa AL, Reichardt P, Robinson MH, Rutkowski P, Safwat AA, Schoffski P, Sleijfer S, Stacchiotti S, Strauss SJ, Sundby Hall K, Unk M, Van Coevorden F, van der Graaf WTA, Whelan J, Wardelmann E, Zaikova O, Blay JY, Esmo Guidelines Committee P, Ern E (2018) Bone sarcomas: ESMO-PaedCan-EURACAN clinical practice guidelines for diagnosis, treatment and follow-up. Annal Oncol 29:79–95
Chen X, Zhao G, Wang F, Gao F, Luo H, Wang Y, Du Y, Chen X, Xue C, Dong Z, Song G (2014) Upregulation of miR-513b inhibits cell proliferation, migration, and promotes apoptosis by targeting high mobility group-box 3 protein in gastric cancer. Tumor Biol 35:11081–11089
Chen B, Wei W, Huang X, Xie X, Kong Y, Dai D, Yang L, Wang J, Tang H, Xie X (2018) circEPSTI1 as a prognostic marker and mediator of triple-negative breast cancer progression. Theranostics 8:4003–4015
Chen KC, Chen PH, Ho KH, Shih CM, Chou CM, Cheng CH, Lee CC (2019) IGF-1-enhanced miR-513a-5p signaling desensitizes glioma cells to temozolomide by targeting the NEDD4L-inhibited Wnt/beta-catenin pathway. PloS one 14:e0225913
Cheng Z, Yu C, Cui S, Wang H, Jin H, Wang C, Li B, Qin M, Yang C, He J, Zuo Q, Wang S, Liu J, Ye W, Lv Y, Zhao F, Yao M, Jiang L, Qin W (2019) circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1. Nat Commun 10:3200
da Silveira MB, Lima KF, da Silva AR, Dos Santos RAS, Moraes KCM (2018) Mir-513a-3p contributes to the controlling of cellular migration processes in the A549 lung tumor cells by modulating integrin beta-8 expression. Mol Cell Biochem 444:43–52
Fan TM, Roberts RD, Lizardo MM (2020) Understanding and modeling metastasis biology to improve therapeutic strategies for combating osteosarcoma progression. Front Oncol 10:13
Hong X, Liu N, Liang Y, He Q, Yang X, Lei Y, Zhang P, Zhao Y, He S, Wang Y, Li J, Li Q, Ma J, Li Y (2020) Circular RNA CRIM1 functions as a ceRNA to promote nasopharyngeal carcinoma metastasis and docetaxel chemoresistance through upregulating FOXQ1. Mol Cancer 19:33
Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J (2019) The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 20:675–691
Liang Y, Zhang Y, Xu L, Zhou D, Jin Z, Zhou H, Lin S, Cao J, Huang L (2019) CircRNA expression pattern and ceRNA and miRNA-mRNA networks involved in anther development in the CMS line of Brassica campestris. Int J Mol Sci. https://doi.org/10.3390/ijms20194808
Lindsey BA, Markel JE, Kleinerman ES (2017) Osteosarcoma overview. Rheumatol Ther 4:25–43
Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25:402–408
Luetke A, Meyers PA, Lewis I, Juergens H (2014) Osteosarcoma treatment—where do we stand? A state of the art review. Cancer Treat Rev 40:523–532
Muti P, Donzelli S, Sacconi A, Hossain A, Ganci F, Frixa T, Sieri S, Krogh V, Berrino F, Biagioni F, Strano S, Beyene J, Yarden Y, Blandino G (2018) MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: the hOrmone and diet in the ETiology of breast cancer prospective study. Carcinogenesis 39:98–108
Patop IL, Kadener S (2018) circRNAs in cancer. Curr Opin Genet Dev 48:121–127
Steliga M, Vaporciyan A (2009) Surgical treatment of pulmonary metastases from osteosarcoma in pediatric and adolescent patients. Cancer Treat Res 152:185–201
Vo JN, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y, Wu YM, Dhanasekaran SM, Engelke CG, Cao X, Robinson DR, Nesvizhskii AI, Chinnaiyan AM (2019) The landscape of circular RNA in cancer. Cell 176:869-881.e13
Wan B, Hu H, Wang R, Liu W, Chen D (2020) Therapeutic potential of circular RNAs in osteosarcoma. Front Oncol 10:370
Wang X, Zhang X, Wang G, Wang L, Lin Y, Sun F (2017) Hsa-miR-513b-5p suppresses cell proliferation and promotes P53 expression by targeting IRF2 in testicular embryonal carcinoma cells. Gene 626:344–353
Wang C, Jing J, Cheng L (2018a) Emerging roles of non-coding RNAs in the pathogenesis, diagnosis and prognosis of osteosarcoma. Invest New Drugs 36:1116–1132
Wang C, Ren M, Zhao X, Wang A, Wang J (2018b) Emerging roles of circular RNAs in osteosarcoma. Med Sci Monit 24:7043–7050
Wang L, Liang Y, Mao Q, Xia W, Chen B, Shen H, Xu L, Jiang F, Dong G (2019) Circular RNA circCRIM1 inhibits invasion and metastasis in lung adenocarcinoma through the microRNA (miR)-182/miR-93-leukemia inhibitory factor receptor pathway. Cancer Sci 110:2960–2972
Yan H, Li H, Silva MA, Guan Y, Yang L, Zhu L, Zhang Z, Li G, Ren C (2019) LncRNA FLVCR1-AS1 mediates miR-513/YAP1 signaling to promote cell progression, migration, invasion and EMT process in ovarian cancer. J Exp Clin Cancer Res 38:356
Yang Z, Li X, Yang Y, He Z, Qu X, Zhang Y (2016) Long noncoding RNAs in the progression, metastasis, and prognosis of osteosarcoma. Cell Death Dis 7:e2389
Zhang SJ, Ma J, Wu JC, Hao ZZ, Zhang YA, Zhang YJ (2020) Circular RNA circCRIM1 suppresses lung adenocarcinoma cell migration, invasion, EMT, and glycolysis through regulating miR-125b-5p/BTG2 axis. Eur Rev Med Pharmacol Sci 24:3761–3774
Zhong Y, Du Y, Yang X, Mo Y, Fan C, Xiong F, Ren D, Ye X, Li C, Wang Y, Wei F, Guo C, Wu X, Li X, Li Y, Li G, Zeng Z, Xiong W (2018) Circular RNAs function as ceRNAs to regulate and control human cancer progression. Mol Cancer 17:79
Zhu KP, Zhang CL, Ma XL, Hu JP, Cai T, Zhang L (2019) Analyzing the interactions of mRNAs and ncRNAs to predict competing endogenous RNA networks in osteosarcoma chemo-resistance. Mol Ther 27:518–530
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare no conflicts of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Wu, P., Kong, Y., Dai, Z. et al. The circular RNA circCRIM1 inhibits osteosarcoma progression through sponging miR-513. Mamm Genome 32, 495–502 (2021). https://doi.org/10.1007/s00335-021-09903-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00335-021-09903-2