Skip to main content
SpringerLink
Log in

MiR-520a-3p inhibits malignant progression of epithelial ovarian cancer by targeting SUV39H1 expression

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Downregulation of microRNA-520a-3p (miR-520a-3p) has been demonstrated in several cancers, and miR-520a-3p has been shown to inhibit tumor progression, indicating its potential role as a tumor suppressor. In this study, we found that miR-520a-3p was also downregulated in epithelial ovarian cancer (EOC) tissues and cell lines. Functional assays showed that ectopic expression of miR-520a-3p suppressed EOC cell proliferation, invasion, and epithelial–mesenchymal transition (EMT) and induced cell cycle arrest in vitro. Similarly, overexpression of miR-520a-3p inhibited tumor growth and metastasis in vivo. Mechanistically, suppressor of variegation 39H1 (SUV39H1) was identified as a novel target of miR-520a-3p through biomedical databases and dual-luciferase reporter assay. Subsequently, SUV39H1 was observed to be negatively regulated by miR-520a-3p at the mRNA and protein levels, and inversely correlated with miR-520a-3p expression in EOC tissues. Furthermore, overexpression of SUV39H1 reversed the suppressive effects of miR-520a-3p in EOC cells. Collectively, these results suggest that the miR-520a-3p/SUV39H1 axis may contribute to EOC cell proliferation and metastasis, revealing miR-520a-3p as a potential therapeutic target for the treatment of EOC.

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

Similar content being viewed by others

References

  1. Huang TT, Lampert EJ, Coots C, et al. Targeting the PI3K pathway and DNA damage response as a therapeutic strategy in ovarian cancer. Cancer Treat Rev. 2020;86:102021.

    Article  CAS  Google Scholar 

  2. Jemal A, Siegel R, Ward E, et al. Cancer statistics 2007. CA Cancer J Clinicians. 2007;57:43–66.

    Article  Google Scholar 

  3. Ahmed N, Kadife E, Raza A, et al. Ovarian cancer, cancer stem cells and current treatment strategies: a potential role of magmas in the current treatment methods. Cells. 2020;9:719.

    Article  CAS  Google Scholar 

  4. Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics, 2018. CA Cancer J Clinicians. 2018;68:284–96.

    Article  Google Scholar 

  5. Prat J. Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features. Virchows Arch. 2012;460:237–49.

    Article  Google Scholar 

  6. Kim S, Han Y, Kim SI, et al. Tumor evolution and chemoresistance in ovarian cancer. NPJ Precis Oncol. 2018;2:20.

    Article  Google Scholar 

  7. Shield K, Ackland ML, Ahmed N, et al. Multicellular spheroids in ovarian cancer metastases: biology and pathology. Gynecol Oncol. 2009;113:143–8.

    Article  Google Scholar 

  8. Li H, Zhu X, Zhang J, et al. MicroRNA-25 inhibits high glucose-induced apoptosis in renal tubular epithelial cells via PTEN/AKT pathway. Biomed Pharmacother. 2017;96:471–9.

    Article  CAS  Google Scholar 

  9. Zhang C. MicroRNomics: a newly emerging approach for disease biology. Physiol Genomics. 2008;33:139–47.

    Article  Google Scholar 

  10. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.

    Article  CAS  Google Scholar 

  11. Tufekci KU, Meuwissen RL, Genc S. The role of microRNAs in biological processes. Methods Mol Biol. 2014;1107:15–31.

    Article  CAS  Google Scholar 

  12. Chen J, Jiang Q, Jiang XQ, et al. miR-146a promoted breast cancer proliferation and invasion by regulating NM23-H1. J Biochem. 2020;167:41–8.

    Article  CAS  Google Scholar 

  13. Zhao G, Wei Z, Guo Y. MicroRNA-107 is a novel tumor suppressor targeting POU3F2 in melanoma. Biol Res. 2020;53:11.

    Article  Google Scholar 

  14. Gao H, Li X, Zhan G, et al. Long noncoding RNA MAGI1-IT1 promoted invasion and metastasis of epithelial ovarian cancer via the miR-200a/ZEB axis. Cell Cycle. 2019;18:1393–406.

    Article  CAS  Google Scholar 

  15. Gong YB, Fan XH. MiR-539-3p promotes the progression of epithelial ovarian cancer by targeting SPARCL1. Eur Rev Med Pharmacol Sci. 2019;23:2366–73.

    PubMed  Google Scholar 

  16. Zhu X, Shen H, Yin X, et al. Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype. J Exp Clin Cancer Res CR. 2019;38:81.

    Article  Google Scholar 

  17. Zhang J, Liu W, Shen F, et al. The activation of microRNA-520h-associated TGF-beta1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression. Cell Death Dis. 2018;9:884.

    Article  Google Scholar 

  18. Yu L, Chen D, Song J. LncRNA SNHG16 promotes non-small cell lung cancer development through regulating EphA2 expression by sponging miR-520a-3p. Thorac Cancer. 2020;11:603–11.

    Article  CAS  Google Scholar 

  19. Pan C, Liu Q, Wu X. HIF1alpha/miR-520a-3p/AKT1/mTOR feedback promotes the proliferation and glycolysis of gastric cancer cells. Cancer Manag Res. 2019;11:10145–56.

    Article  CAS  Google Scholar 

  20. Qu X, Yang L, Shi Q, et al. Lidocaine inhibits proliferation and induces apoptosis in colorectal cancer cells by upregulating mir-520a-3p and targeting EGFR. Pathol Res Pract. 2018;214:1974–9.

    Article  CAS  Google Scholar 

  21. Bi CL, Zhang YQ, Li B, et al. MicroRNA-520a-3p suppresses epithelial-mesenchymal transition, invasion, and migration of papillary thyroid carcinoma cells via the JAK1-mediated JAK/STAT signaling pathway. J Cell Physiol. 2019;234:4054–67.

    Article  CAS  Google Scholar 

  22. Zhang B, Yu L, Han N, et al. LINC01116 targets miR-520a-3p and affects IL6R to promote the proliferation and migration of osteosarcoma cells through the Jak-stat signaling pathway. Biomed Pharmacother. 2018;107:270–82.

    Article  CAS  Google Scholar 

  23. Li J, Wei J, Mei Z, et al. Suppressing role of miR-520a-3p in breast cancer through CCND1 and CD44. Am J Transl Res. 2017;9:146–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Yang C, Kim HS, Park SJ, et al. Inhibition of miR-214–3p aids in preventing epithelial ovarian cancer malignancy by increasing the expression of LHX6. Cancers. 2019;11:1917.

    Article  CAS  Google Scholar 

  25. Zhang Z, Zhang L, Wang B, et al. MiR-337-3p suppresses proliferation of epithelial ovarian cancer by targeting PIK3CA and PIK3CB. Cancer Lett. 2020;469:54–67.

    Article  CAS  Google Scholar 

  26. Yang C, Li H, Zhang T, et al. miR-200c overexpression inhibits the invasion and tumorigenicity of epithelial ovarian cancer cells by suppressing lncRNA HOTAIR in mice. J Cell Biochem. 2020;121:1514–23.

    Article  CAS  Google Scholar 

  27. Li J, Shao W, Feng H. MiR-542–3p, a microRNA targeting CDK14, suppresses cell proliferation, invasiveness, and tumorigenesis of epithelial ovarian cancer. Biomed Pharmacother. 2019;110:850–6.

    Article  CAS  Google Scholar 

  28. Lv X, Li CY, Han P, et al. MicroRNA-520a-3p inhibits cell growth and metastasis of non-small cell lung cancer through PI3K/AKT/mTOR signaling pathway. Eur Rev Med Pharmacol Sci. 2018;22:2321–7.

    CAS  PubMed  Google Scholar 

  29. Peters AH, O’Carroll D, Scherthan H, et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell. 2001;107:323–37.

    Article  CAS  Google Scholar 

  30. Yu T, Wang C, Yang J, et al. Metformin inhibits SUV39H1-mediated migration of prostate cancer cells. Oncogenesis. 2017;6:e324.

    Article  CAS  Google Scholar 

  31. Fan DN, Tsang FH, Tam AH, et al. Histone lysine methyltransferase, suppressor of variegation 3–9 homolog 1, promotes hepatocellular carcinoma progression and is negatively regulated by microRNA-125b. Hepatology. 2013;57:637–47.

    Article  CAS  Google Scholar 

  32. Liu H, Ma Y, Liu C, et al. Reduced miR-125a-5p level in non-small-cell lung cancer is associated with tumour progression. Open Biol. 2018;8:180118.

    Article  Google Scholar 

  33. Cai M, Chen Q, Shen J, et al. Epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1 in gastric cancer. J Cell Mol Med. 2018;22:4721–31.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by grants from the Science and Technology Innovation Fund of Jinshan District of Shanghai (2018-3-04).

Author information

Authors and Affiliations

  1. Department of Gynaecology and Obstetrics, Jinshan Hospital affiliated to Fudan University, No.1508 Longhang Road, Shanghai, 201508, China

    Jingwei Li, Wei Shao & Junhong Zhao

Authors
  1. Jingwei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wei Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junhong Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junhong Zhao.

Ethics declarations

Conflict of interest

The authors confirm that there are no conflicts of interest.

Ethical standards

All animal experiments were performed in accordance with the institutional guidelines from the Care and Use of Laboratory Animals of Jinshan Hospital affiliated to Fudan University and were approved by the Institutional Animal Ethics Committee (2018-30-02).

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, J., Shao, W. & Zhao, J. MiR-520a-3p inhibits malignant progression of epithelial ovarian cancer by targeting SUV39H1 expression. Human Cell 34, 570–578 (2021). https://doi.org/10.1007/s13577-020-00455-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13577-020-00455-2

Keywords

Search

Navigation