Skip to main content
SpringerLink
Log in

EIF4A3-induced circCCNB1 (hsa_circ_0001495) promotes glioma progression by elevating CCND1 through interacting miR-516b-5p and HuR

  • Original Article
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

To explore the functions of circRNA cyclin B1 (circCCNB1) in glioma and its possible mechanisms. The expression of circCCNB1, eukaryotic translation initiation factor 4A3 (EIF4A3), cyclin D1 (CCND1) and miR-516b-5p was determined by qRT-PCR, western blot or immunohistochemistry (IHC) assay. The feature of circCCNB1 was analyzed by Actinomycin D (ActD), RNase R and subcellular fraction assays. The molecule relationships were analyzed by RIP, dual-luciferase reporter and RNA pull-down assays. CCK-8, EdU and colony formation assays were performed to analyze cell proliferation. Flow cytometry analysis was executed to estimate the cell cycle. Murine xenograft model assay was used for the role of circCCNB1 in vivo. CircCCNB1 was overexpressed in glioma tissues and cells. EIF4A3 positively regulated circCCNB1 expression. CircCCNB1 knockdown repressed glioma cell proliferation and cell cycle process in vitro and blocked tumor growth in vivo. CircCCNB1 knockdown reduced CCND1 expression in glioma cells and CCND1 overexpression bated the effect of circCCNB1 knockdown on glioma cell growth. CircCCNB1 interacted with HuR to elevate CCND1 expression. miR-516b-5p could interact with circCCNB1 and CCND1. CircCCNB1 regulated glioma cell progression and CCND1 expression by miR-516b-5p and HuR. CircCCNB1 aggravated glioma cell growth by elevating CCND1 through targeting miR-516b-5p and HuR.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

Data availability

The data used to support the findings of this study are included in the article.

References

  • Abdelmohsen K, Panda AC, Munk R, Grammatikakis I, Dudekula DB, De S et al (2017) Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol 14(3):361–369

    Article  Google Scholar 

  • Bush NA, Chang SM, Berger MS (2017) Current and future strategies for treatment of glioma. Neurosurg Rev 40(1):1–14

    Article  Google Scholar 

  • Cahill D, Turcan S (2018) Origin of Gliomas. Semin Neurol 38(1):5–10

    Article  Google Scholar 

  • Chan CC, Dostie J, Diem MD, Feng W, Mann M, Rappsilber J et al (2004) eIF4A3 is a novel component of the exon junction complex. RNA 10(2):200–209

    Article  CAS  Google Scholar 

  • Chen LL, Yang L (2015) Regulation of circRNA biogenesis. RNA Biol 12(4):381–388

    Article  Google Scholar 

  • Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA et al (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160(6):1125–1134

    Article  CAS  Google Scholar 

  • Furnari FB, Fenton T, Bachoo RM, Mukasa A, Stommel JM, Stegh A et al (2007) Malignant astrocytic glioma: genetics, biology, and paths to treatment. Genes Dev 21(21):2683–2710

    Article  CAS  Google Scholar 

  • Garcia-Maurino SM, Rivero-Rodriguez F, Velazquez-Cruz A, Hernandez-Vellisca M, Diaz-Quintana A, De la Rosa MA et al (2017) RNA Binding Protein Regulation and Cross-Talk in the Control of AU-rich mRNA Fate. Front Mol Biosci 4:71

    Article  Google Scholar 

  • Ghosh U, Adhya S (2018) Posttranscriptional regulation of cyclin D1 by ARE-binding proteins AUF1 and HuR in cycling myoblasts. J Biosci 43(4):685–691

    Article  CAS  Google Scholar 

  • Han C, Wang S, Wang H, Zhang J (2020) Knockdown of circ-TTBK2 inhibits glioma progression by regulating miR-1283 and CHD1. Cancer Manag Res 12:10055–10065

    Article  CAS  Google Scholar 

  • Heinonen M, Fagerholm R, Aaltonen K, Kilpivaara O, Aittomaki K, Blomqvist C et al (2007) Prognostic role of HuR in hereditary breast cancer. Clin Cancer Res 13(23):6959–6963

    Article  CAS  Google Scholar 

  • Huang Y, Jiang L, Wei G (2021) Circ_0006168 promotes the migration, invasion and proliferation of esophageal squamous cell carcinoma cells via miR-516b-5p-dependent regulation of XBP1. Onco Targets Ther 14:2475–2488

    Article  Google Scholar 

  • Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6(6):590–610

    Article  CAS  Google Scholar 

  • Liu B, Yang G, Wang X, Liu J, Lu Z, Wang Q et al (2020a) CircBACH1 (hsa_circ_0061395) promotes hepatocellular carcinoma growth by regulating p27 repression via HuR. J Cell Physiol 235(10):6929–6941

    Article  CAS  Google Scholar 

  • Liu J, Hou K, Ji H, Mi S, Yu G, Hu S et al (2020b) Overexpression of circular RNA circ-CDC45 facilitates glioma cell progression by sponging miR-516b and miR-527 and predicts an adverse prognosis. J Cell Biochem 121(1):690–697

    Article  CAS  Google Scholar 

  • Liu NZ, Li T, Liu CM, Liu FR, Wang YX (2020c) Hsa_circ_0000337 promotes proliferation, migration and invasion in glioma by competitively binding miRNA-942-5p and thus upregulates MAT2A. Eur Rev Med Pharmacol Sci 24(23):12251–12257

    PubMed  Google Scholar 

  • Liu H, Lan T, Li H, Xu L, Chen X, Liao H et al (2021) Circular RNA circDLC1 inhibits MMP1-mediated liver cancer progression via interaction with HuR. Theranostics 11(3):1396–1411

    Article  Google Scholar 

  • Lopez de Silanes I, Fan J, Yang X, Zonderman AB, Potapova O, Pizer ES et al (2003) Role of the RNA-binding protein HuR in colon carcinogenesis. Oncogene 22(46):7146–7154

    Article  CAS  Google Scholar 

  • Ng WL, Mohd Mohidin TB, Shukla K (2018) Functional role of circular RNAs in cancer development and progression. RNA Biol 15(8):995–1005

    PubMed  PubMed Central  Google Scholar 

  • Ostrom QT, Gittleman H, Stetson L, Virk SM, Barnholtz-Sloan JS (2015) Epidemiology of gliomas. Cancer Treat Res 163:1–14

    Article  Google Scholar 

  • Patop IL, Wust S, Kadener S (2019) Past, present, and future of circRNAs. EMBO J 38(16):e100836

    Article  Google Scholar 

  • Shen H, Xu L, You C, Tang H, Wu H, Zhang Y et al (2021) miR-665 is downregulated in glioma and inhibits tumor cell proliferation, migration and invasion by targeting high mobility group box 1. Oncol Lett 21(2):156

    Article  CAS  Google Scholar 

  • Sotoudeh H, Shafaat O, Bernstock JD, Brooks MD, Elsayed GA, Chen JA et al (2019) Artificial Intelligence in the Management of Glioma: Era of Personalized Medicine. Front Oncol 9:768

    Article  Google Scholar 

  • Wang Y, Mo Y, Gong Z, Yang X, Yang M, Zhang S et al (2017) Circular RNAs in human cancer. Mol Cancer 16(1):25

    Article  CAS  Google Scholar 

  • Wang L, Shang X, Feng Q (2019) LncRNA TATDN1 contributes to the cisplatin resistance of non-small cell lung cancer through TATDN1/miR-451/TRIM66 axis. Cancer Biol Ther 20(3):261–271

    Article  CAS  Google Scholar 

  • Wang T, Zhang Y, Cui B, Wang M, Li Y, Gao K (2020a) miR-4530 inhibits the malignant biological behaviors of human glioma cells by directly targeting RTEL1. Acta Biochim Biophys Sin (Shanghai) 52(12):1394–1403

    Article  CAS  Google Scholar 

  • Wang X, Feng H, Dong W, Wang F, Zhang G, Wu J (2020b) Hsa_circ_0008225 inhibits tumorigenesis of glioma via sponging miR-890 and promoting ZMYND11 expression. J Pharmacol Sci 143(2):74–82

    Article  CAS  Google Scholar 

  • Wang X, Zhu Y (2021) Circ_0000020 elevates the expression of PIK3CA and facilitates the malignant phenotypes of glioma cells via targeting miR-142-5p. Cancer Cell Int 21(1):79

    Article  Google Scholar 

  • Xie P, Han Q, Liu D, Yao D, Lu X, Wang Z et al (2020) miR-525-5p modulates proliferation and epithelial-mesenchymal transition of glioma by targeting stat-1. Onco Targets Ther 13:9957–9966

    Article  CAS  Google Scholar 

  • Xie Y, Liu X, Hu T, Wang W (2020) miR-302e suppresses glioma progression by targeting VEGFA. Cancer Manag Res 12:10965–10974

    Article  CAS  Google Scholar 

  • Zang Y, Li J, Wan B, Tai Y (2020) circRNA circ-CCND1 promotes the proliferation of laryngeal squamous cell carcinoma through elevating CCND1 expression via interacting with HuR and miR-646. J Cell Mol Med 24(4):2423–2433

    Article  CAS  Google Scholar 

  • Zuo CY, Qian W, Huang CJ, Lu J (2019) Circular RNA circ-SMAD7 promoted glioma cell proliferation and metastasis by upregulating PCNA. Eur Rev Med Pharmacol Sci 23(22):10035–10041

    PubMed  Google Scholar 

  • Zhou H, Zhang Y, Lai Y, Xu C, Cheng Y (2020) Circ_101064 regulates the proliferation, invasion and migration of glioma cells through miR-154-5p/ PIWIL1 axis. Biochem Biophys Res Commun 523(3):608–614

    Article  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Xiaoli Li and Chengmou Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Neurology, Renmin Hospital, Hubei University of Medicine, No. 39, Chaoyang Middle Road, Maojian District, Shiyan, 442000, China

    Xiaoli Li, Chengmou Wang, Guanghui Chen, Wenqin Zou, Yanqing Deng & Faming Zhou

Authors
  1. Xiaoli Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chengmou Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Guanghui Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenqin Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanqing Deng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Faming Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Faming Zhou designed and supervised the study. Xiaoli Li and Chengmou Wang conducted the experiments and drafted the manuscript. Guanghui Chen and Wenqin Zou collected and analyzed the data. Yanqing Deng contributed the methodology, operated the software and edited the manuscript.

Corresponding author

Correspondence to Faming Zhou.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethics approval and consent to participate

The project was authorized by the Ethics Committee of Renmin Hospital, Hubei University of Medicine. All participants provided written informed consents.

The Ethics Committee of Animal Research of Renmin Hospital, Hubei University of Medicine approved the animal study.

Consent for publication

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Wang, C., Chen, G. et al. EIF4A3-induced circCCNB1 (hsa_circ_0001495) promotes glioma progression by elevating CCND1 through interacting miR-516b-5p and HuR. Metab Brain Dis 37, 819–833 (2022). https://doi.org/10.1007/s11011-021-00899-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11011-021-00899-x

Keywords

Search

Navigation