Abstract
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. Increasing evidence suggests that aberrant expression of circRNAs is associated with the occurrence and progression of many cancers. Here, we investigated the role of circNRIP1 in osteosarcoma and explored its possible underlying mechanisms. Three pairs of osteosarcoma tissues and adjacent normal tissues were applied to the detection of altered expression of circRNAs through circRNAs microarray. And the level of circNRIP1 expression was elevated in osteosarcoma tissues. Compared with that in adjacent normal tissue, circNRIP1 expression level was obviously elevated in 100 osteosarcoma tissues. Besides, circNRIP1 knockdown inhibited proliferation and migration, promoted apoptosis of osteosarcoma cells. Bioinformatic analysis demonstrated circNRIP1 contributed to FOXC2 expression by sponging miR-199a. Furthermore, METTL3 elevated circNRIP1 expression level via m6A modification. In short, METTL3-induced circNRIP1 exerted an oncogenic role in osteosarcoma by sponging miR-199a, which may provide new ideas for the treatment of osteosarcoma.
Similar content being viewed by others
Data availability
The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
References
Ambros V (2004) The functions of animal microRNAs. Nature 431:350–355
Chen LL, Yang L (2015) Regulation of circRNA biogenesis. RNA Biol 12:381–388
Chen Y, Lin Y, Shu Y, He J, Gao W (2020) Interaction between N(6)-methyladenosine (m(6)A) modification and noncoding RNAs in cancer. Mol Cancer 19:94
Desrosiers R, Friderici K, Rottman F (1974) Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci U S A 71:3971–3975
Dong Z, Liu Y, Wang Q, Wang H, Ji J, Huang T, Khanal A, Niu H, Cao Y (2020) The circular RNA-NRIP1 plays oncogenic roles by targeting microRNA-505 in the renal carcinoma cell lines. J Cell Biochem 121:2236–2246
Duan Z, Choy E, Harmon D, Liu X, Susa M, Mankin H, Hornicek F (2011) MicroRNA-199a-3p is downregulated in human osteosarcoma and regulates cell proliferation and migration. Mol Cancer Ther 10:1337–1345
Fu Y, Dominissini D, Rechavi G, He C (2014) Gene expression regulation mediated through reversible m(6)A RNA methylation. Nat Rev Genet 15:293–306
Han B, Chao J, Yao H (2018) Circular RNA and its mechanisms in disease: from the bench to the clinic. Pharmacol Ther 187:31–44
Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388
Hollier BG, Tinnirello AA, Werden SJ, Evans KW, Taube JH, Sarkar TR, Sphyris N, Shariati M, Kumar SV, Battula VL, Herschkowitz JI, Guerra R, Chang JT, Miura N, Rosen JM, Mani SA (2013) FOXC2 expression links epithelial-mesenchymal transition and stem cell properties in breast cancer. Cancer Res 73:1981–1992
Huang X, Zhao J, Bai J, Shen H, Zhang B, Deng L, Sun C, Liu Y, Zhang J, Zheng J (2019) Risk and clinicopathological features of osteosarcoma metastasis to the lung: a population-based study. J Bone Oncol 16:e100230
Jeck WR, Sharpless NE (2014) Detecting and characterizing circular RNAs. Nat Biotechnol 32:453–461
Kansara M, Teng MW, Smyth MJ, Thomas DM (2014) Translational biology of osteosarcoma. Nat Rev Cancer 14:722–735
Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610
Lasda E, Parker R (2014) Circular RNAs: diversity of form and function. RNA 20:1829–1842
Li W, Fu X, Liu R, Wu C, Bai J, Xu Y, Zhao Y (2013) FOXC2 often overexpressed in glioblastoma enhances proliferation and invasion in glioblastoma cells. Oncol Res 21:111–120
Li J, Han Y, Zhang H, Qian Z, Jia W, Gao Y, Zheng H, Li B (2019) The m6A demethylase FTO promotes the growth of lung cancer cells by regulating the m6A level of USP7 mRNA. Biochem Biophys Res Commun 512:479–485
Li X, Ma N, Zhang Y, Wei H, Zhang H, Pang X, Wu D, Wang D, Yang Z, Zhang S (2020) Circular RNA circNRIP1 promotes migration and invasion in cervical cancer by sponging miR-629-3p and regulating the PTP4A1/ERK1/2 pathway. Cell Death Dis 11:399
Lindsey BA, Markel JE, Kleinerman ES (2017) Osteosarcoma overview. Rheumatol Ther 4:25–43
Liu Y, Jiang Y, Xu L, Qu C, Zhang L, Xiao X, Chen W, Li K, Liang Q, Wu H (2020) circ-NRIP1 promotes glycolysis and tumor progression by regulating miR-186-5p/MYH9 axis in gastric cancer. Cancer Manag Res 12:5945–5956
Miao W, Chen J, Jia L, Ma J, Song D (2019) The m6A methyltransferase METTL3 promotes osteosarcoma progression by regulating the m6A level of LEF1. Biochem Biophys Res Commun 516:719–725
Mirabello L, Troisi RJ, Savage SA (2009) International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 125:229–234
Miura N, Wanaka A, Tohyama M, Tanaka K (1993) MFH-1, a new member of the fork head domain family, is expressed in developing mesenchyme. FEBS Lett 326:171–176
Nishida N, Mimori K, Yokobori T, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Mori M (2011) FOXC2 is a novel prognostic factor in human esophageal squamous cell carcinoma. Ann Surg Oncol 18:535–542
Panni S, Lovering RC, Porras P, Orchard S (2020) Non-coding RNA regulatory networks. Biochim Biophys Acta Gene Regul Mech 1863:e194417
Rybak-Wolf A, Stottmeister C, Glazar P, Jens M, Pino N, Giusti S, Hanan M, Behm M, Bartok O, Ashwal-Fluss R, Herzog M, Schreyer L, Papavasileiou P, Ivanov A, Ohman M, Refojo D, Kadener S, Rajewsky N (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58:870–885
Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO (2013) Cell-type specific features of circular RNA expression. PLoS Genet 9:e1003777
Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK (1976) Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A 73:3852–3856
Shang Q, Yang Z, Jia R, Ge S (2019) The novel roles of circRNAs in human cancer. Mol Cancer 18:6
Siegel RL, Miller KD, Jemal A (2020) Cancer statistics, 2020. CA Cancer J Clin 70:7–30
Slack FJ, Chinnaiyan AM (2019) the role of non-coding RNAs in oncology. Cell 179:1033–1055
Tian R, Xie X, Han J, Luo C, Yong B, Peng H, Shen J, Peng T (2014) miR-199a-3p negatively regulates the progression of osteosarcoma through targeting AXL. Am J Cancer Res 4:738–750
Vo JN, Cieslik M, Zhang Y, Shukla S, Xiao L, 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):e813
Zhang Z, Yang T, Xiao J (2018) Circular RNAs: promising biomarkers for human diseases. EBioMedicine 34:267–274
Zhang X, Wang S, Wang H, Cao J, Huang X, Chen Z, Xu P, Sun G, Xu J, Lv J, Xu Z (2019) Circular RNA circNRIP1 acts as a microRNA-149-5p sponge to promote gastric cancer progression via the AKT1/mTOR pathway. Mol Cancer 18:20
Zhang L, Hou C, Chen C, Guo Y, Yuan W, Yin D, Liu J, Sun Z (2020) The role of N(6)-methyladenosine (m(6)A) modification in the regulation of circRNAs. Mol Cancer 19:105
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
Zhou L, Yang C, Zhang N, Zhang X, Zhao T, Yu J (2020) Silencing METTL3 inhibits the proliferation and invasion of osteosarcoma by regulating ATAD2. Biomed Pharmacother 125:e109964
Acknowledgements
This work was supported by Hong Hui Hospital.
Funding
No.
Author information
Authors and Affiliations
Contributions
YM and DJH designed experiments; YFH, SJJ and JNZ performed experiments; XRH and DL analyzed the data; LS wrote the manuscript. All authors read and approved the manuscript.
Corresponding authors
Ethics declarations
Conflict of interests
Yibin Meng, DingJun Hao, YunFei Huang, ShuaiJun Jia, JiaNan Zhang, XiRui He, Deyin Liu, and Liang Sun declare that they have no conflict of interest.
Ethical approval
This study was approved by the ethics committee of Hong Hui Hospital.
Informed consent
All patients gave informed consent.
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
Meng, Y., Hao, D., Huang, Y. et al. Circular RNA circNRIP1 plays oncogenic roles in the progression of osteosarcoma. Mamm Genome 32, 448–456 (2021). https://doi.org/10.1007/s00335-021-09891-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00335-021-09891-3