Skip to main content
SpringerLink
Log in

CircDHDDS/miR-361-3p/WNT3A Axis Promotes the Development of Retinoblastoma by Regulating Proliferation, Cell Cycle, Migration, and Invasion of Retinoblastoma Cells

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Retinoblastoma (RB) is a common intraocular malignant tumor. The growing evidence has reported that circular RNAs (circRNAs) play critical roles in RB development. Therefore, the purpose of the study is to investigate the regulatory mechanism of circDHDDS in RB. The real-time quantitative polymerase chain reaction (RT-qPCR) assay was used to quantify the expression levels of circDHDDS, miR-361-3p, and WNT3A in RB tissues and cells (RPCs, Y-79, and WERI-Rb-1). The proliferation and cell cycle of RB cells were assessed by colony formation assay and flow cytometry assays, respectively. The migration and invasion of RB cells were measured by transwell assay. The protein expression levels of Nectin-3 (CD113), SOX2, Nanog, and WNT3A were measured by Western blot assay. The functional targets of circDHDDS and miR-361-3p were predicted by bioinformatics databases, and the dual-luciferase reporter assay was used to confirm the interaction relationship between miR-361-3p and circDHDDS or WNT3A. The functional role of circDHDDS silencing in vivo was evaluated by xenograft experiment. We found that circDHDDS was overexpressed in RB tissues and cells compared with normal retinas tissues and retinal pigment epithelial cells, correspondingly. Furthermore, silencing of circDHDDS impeded proliferation, migration, invasion, and induced cell cycle arrest in vitro, which were abolished by knockdown of miR-361-3p. The in vivo experiments also suggested that tumor growth was inhibited by knockdown of circDHDDS. Moreover, we also found that miR-361-3p specifically bound to WNT3A, and overexpression of miR-361-3p suppressed RB development by decreasing WNT3A expression. Summarily, circDHDDS, a molecule sponge of miR-361-3p, regulated the expression of WNT3A. Therefore, circDHDDS/miR-361-3p/WNT3A axis stimulated the development of RB by regulation of proliferation, cell cycle program, migration, and invasion of RB cells.

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

Similar content being viewed by others

Data Availability

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

Abbreviations

RB:

Retinoblastoma

circRNA:

Circular RNA

RT-qPCR:

Real-time quantitative polymerase chain reaction

References

  1. Kivelä TT, Hadjistilianou T (2017) Neonatal retinoblastoma. Asia Pac J Oncol Nurs 4:197–204

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ahmad A (2016) Retinoblastoma-clinical spectrum and treatment outcome in children. J Rawalpindi Med Coll 20:198–201

    Google Scholar 

  3. Gao J, Zeng J, Guo B, He W, Chen J, Lu F et al (2016) Clinical presentation and treatment outcome of retinoblastoma in children of South Western China. Medicine 95:e5204

    Article  PubMed  PubMed Central  Google Scholar 

  4. Waddell KM, Kagame K, Ndamira A, Twinamasiko A, Picton SV, Simmons IG et al (2015) Clinical features and survival among children with retinoblastoma in Uganda. Br J Ophthalmol 99:387–390

    Article  PubMed  Google Scholar 

  5. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333

    Article  CAS  PubMed  Google Scholar 

  6. Yu T, Wang Y, Fan Y, Fang N, Wang T, Xu T et al (2019) CircRNAs in cancer metabolism: a review. J Hematol Oncol 12:90

    Article  PubMed  PubMed Central  Google Scholar 

  7. Zhu L-P, He Y-J, Hou J-C, Chen X, Zhou S-Y, Yang S-J et al (2017) The role of circRNAs in cancers. Biosci Rep 37:BSR20170750

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lyu J, Wang Y, Zheng Q, Hua P, Zhu X, Li J et al (2019) Reduction of circular RNA expression associated with human retinoblastoma. Exp Eye Res 184:278–285

    Article  PubMed  Google Scholar 

  9. Schirle NT, Sheu-Gruttadauria J, MacRae IJ (2014) Structural basis for microRNA targeting. Science 346(6209):608–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Farazi TA, Spitzer JI, Morozov P, Tuschl T (2011) miRNAs in human cancer. J Pathol 223:102–115

    Article  CAS  PubMed  Google Scholar 

  11. Chen W, Wang J, Liu S, Wang S, Cheng Y, Zhou W et al (2016) MicroRNA-361-3p suppresses tumor cell proliferation and metastasis by directly targeting SH2B1 in NSCLC. J Exp Clin Cancer Res 35:76

    Article  PubMed  PubMed Central  Google Scholar 

  12. Liu S, Song L, Yao H, Zhang L, Xu D, Li Q et al (2018) Preserved miR-361-3p expression is an independent prognostic indicator of favorable survival in cervical cancer. Dis Mark. https://doi.org/10.1155/2018/8949606

    Article  Google Scholar 

  13. Zhao D, Cui Z (2019) MicroRNA-361-3p regulates retinoblastoma cell proliferation and stemness by targeting hedgehog signaling. Exp Ther Med 17:1154–1162

    CAS  PubMed  Google Scholar 

  14. Dzobo K, Thomford NE, Senthebane DA (2019) Targeting the versatile Wnt/β-catenin pathway in cancer biology and therapeutics: from concept to actionable strategy. OMICS 23(11):517–538

    Article  CAS  PubMed  Google Scholar 

  15. Liao YJ, Yin XL, Deng Y (2019) Peng XW (2019) PRC1 gene silencing inhibits proliferation, invasion, and angiogenesis of retinoblastoma cells through the inhibition of the Wnt/β-catenin signaling pathway. J Cell Biochem 120(10):16840–16852

    Article  CAS  PubMed  Google Scholar 

  16. Yun M-S, Kim S-E, Jeon SH, Lee J-S, Choi K-Y (2005) Both ERK and Wnt/β-catenin pathways are involved in Wnt3a-induced proliferation. J Cell Sci 118:313–322

    Article  CAS  PubMed  Google Scholar 

  17. He S, Lu Y, Liu X, Huang X, Keller ET, Qian C-N et al (2015) Wnt3a: functions and implications in cancer. Chin J Cancer 34:50

    Article  PubMed Central  Google Scholar 

  18. Zhang S, Chen X, Hu Y, Wu J, Cao Q, Chen S et al (2016) All-trans retinoic acid modulates Wnt3A-induced osteogenic differentiation of mesenchymal stem cells via activating the PI3K/AKT/GSK3β signalling pathway. Mol Cell Endocrinol 422:243–253

    Article  CAS  PubMed  Google Scholar 

  19. Ni H, Chai P, Yu J, Xing Y, Wang S, Fan J et al (2020) LncRNA CANT1 suppresses retinoblastoma progression by repellinghistone methyltransferase in PI3Kγ promoter. Cell Death Dis 11(5):306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pan Y, Ma S, Cao K et al (2018) Therapeutic approaches targeting cancer stem cells. J Cancer Res Ther 14(7):1469–1475

    Article  CAS  PubMed  Google Scholar 

  21. Wang Z, Zhao Y, Wang Y, Jin C (2019) Circular RNA circHIAT1 inhibits cell growth in hepatocellular carcinoma by regulating miR-3171/PTEN axis. Biomed Pharmacother 116:108932

    Article  CAS  PubMed  Google Scholar 

  22. Rong D, Sun H, Li Z, Liu S, Dong C, Fu K et al (2017) An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget 8:73271

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  24. Kim P, Park A, Han G, Sun H, Jia P, Zhao Z (2018) TissGDB: tissue-specific gene database in cancer. Nucleic Acids Res 46(D1):D1031–D1038

    Article  CAS  PubMed  Google Scholar 

  25. Peter ME (2010) Targeting of mRNAs by multiple miRNAs: the next step. Oncogene 29(15):2161–2164

    Article  CAS  PubMed  Google Scholar 

  26. Hu J, Li L, Chen H, Zhang G, Liu H, Kong R et al (2018) MiR-361-3p regulates ERK1/2-induced EMT via DUSP2 mRNA degradation in pancreatic ductal adenocarcinoma. Cell Death Dis 9:807

    Article  PubMed  PubMed Central  Google Scholar 

  27. Ogawa H, Nakashiro KI, Tokuzen N, Kuribayashi N, Goda H, Uchida D (2020) MicroRNA-361-3p is a potent therapeutic target for oral squamous cell carcinoma. Cancer Sci 111(5):1645–1651

  28. Pan L-H, Yao M, Cai Y, Gu J-J, Yang X-L, Wang L et al (2016) Oncogenic Wnt3a expression as an estimable prognostic marker for hepatocellular carcinoma. World J Gastroenterol 22:3829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Qi L, Sun B, Liu Z, Cheng R, Li Y, Zhao X (2014) Wnt3a expression is associated with epithelial-mesenchymal transition and promotes colon cancer progression. J Exp Clin Cancer Res 33:107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhang B, Wang Q, Pan X (2007) MicroRNAs and their regulatory roles in animals and plants. J Cell Physiol 210:279–289

    Article  CAS  PubMed  Google Scholar 

  31. Lyu X, Wang L, Lu J, Zhang H, Wang L (2019) microRNA-485 inhibits the malignant behaviors of retinoblastoma by directly targeting Wnt3a. Oncol Rep 41:3137–3147

    CAS  PubMed  Google Scholar 

  32. Yang Y, Zhao Z, Hou N, Li Y, Wang X, Wu F et al (2017) MicroRNA-214 targets Wnt3a to suppress liver cancer cell proliferation. Mol Med Rep 16:6920–6927

    Article  CAS  PubMed  Google Scholar 

  33. Kaur N, Chettiar S, Rathod S, Rath P, Muzumdar D, Shaikh M et al (2013) Wnt3a mediated activation of Wnt/β-catenin signaling promotes tumor progression in glioblastoma. Mol Cell Neurosci 54:44–57

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

No funding was received.

Author information

Authors and Affiliations

  1. Department of Medical Administration, Shanghai Pudong Hospital, Shanghai, China

    Hongjun Wang

  2. Department of Ophthalmology, Shanghai Pudong Hospital, Shanghai, China

    Mingze Li, Xiangyuan Song & Qian Sha

  3. Department of Ophthalmology, Heilongjiang Eye Hospital, Harbin, Heilongjiang, China

    Haibin Cui

Authors
  1. Hongjun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingze Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haibin Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiangyuan Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qian Sha
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization and Methodology: ML and HC; Formal analysis and Data curation: XS and QS; Validation and Investigation: HW and XS; Writing—original draft preparation and Writing—review and editing: HW, ML and HC; Approval of final manuscript: all authors.

Corresponding author

Correspondence to Qian Sha.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Ethical Approval

The present study was approved by the ethical review committee of The Second Hospital of Hebei Medical University.

Informed Consent

Written informed consent was obtained from all enrolled patients.

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

Wang, H., Li, M., Cui, H. et al. CircDHDDS/miR-361-3p/WNT3A Axis Promotes the Development of Retinoblastoma by Regulating Proliferation, Cell Cycle, Migration, and Invasion of Retinoblastoma Cells. Neurochem Res 45, 2691–2702 (2020). https://doi.org/10.1007/s11064-020-03112-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-020-03112-0

Keywords

Search

Navigation