Skip to main content
Log in

MicroRNA-377-3p inhibits growth and invasion through sponging JAG1 in ovarian cancer

  • Research Article
  • Published:
Genes & Genomics Aims and scope Submit manuscript



Ovarian cancer is the one of the most deadly gynecologic malignancy among cancer related death in women. However, the treatment for ovarian cancer is still limited. In this study, we aimed to explore the inhibition potential of miR-377-3p in ovarian cancer and explore the mechanism of this effect.


Quantitative real-time PCR was used to detect the mRNA or microRNA (miRNA) levels. CCK-8, wound-healing, transwell assay were used to detect cell proliferation, migration and invasion. The protein levels were examined by western blot. The dual luciferase reporter assay was conducted to examine the luciferase activity. Tumor volume was measured and Ki67 was detected via immunohistochemistry.


qRT-PCR results showed that miR-377-3p was downregulated in ovarian cancer patients. MiR-377-3p mimics suppressed cell proliferation, migration, invasion and decreased the JAG1 level. However, miR-377-3p inhibitor promoted these appearances. Interestingly, we found JAG1 was a target gene of miR-377-3p. JAG1 overexpression reversed the miR-377-3p-induced inhibition of proliferation and invasion. In addition, miR-377-3p inhibited ovarian cancer tumorigenesis in vivo, indicating by decreased tumor volume and staining of Ki67.


The results showed that miR-377-3p inhibited growth and invasion of ovarian cancer cells by targeting JAG1.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others


  • Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  • Bellon M, Moles R, Chaib-Mezrag H, Pancewicz J, Nicot C (2018) JAG1 overexpression contributes to Notch1 signaling and the migration of HTLV-1-transformed ATL cells. J Hematol Oncol 11:119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang WH, Ho BC, Hsiao YJ, Chen JS, Yeh CH, Chen HY, Chang GC, Su KY, Yu SL (2016) JAG1 is associated with poor survival through inducing metastasis in lung cancer. PLoS ONE 11:e0150355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen X, Stoeck A, Lee SJ, Shih Ie M, Wang MM, Wang TL (2010) Jagged1 expression regulated by Notch3 and Wnt/beta-catenin signaling pathways in ovarian cancer. Oncotarget 1:210–218

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen J, Zhang H, Chen Y, Qiao G, Jiang W, Ni P, Liu X, Ma L (2017) miR-598 inhibits metastasis in colorectal cancer by suppressing JAG1/Notch2 pathway stimulating EMT. Exp Cell Res 352:104–112

    Article  CAS  PubMed  Google Scholar 

  • Choi JH, Park JT, Davidson B, Morin PJ, Shih Ie M, Wang TL (2008) Jagged-1 and Notch3 juxtacrine loop regulates ovarian tumor growth and adhesion. Cancer Res 68:5716–5723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo J, Zhang CD, An JX, Xiao YY, Shao S, Zhou NM, Dai DQ (2018) Expression of miR-634 in gastric carcinoma and its effects on proliferation, migration, and invasion of gastric cancer cells. Cancer Med 7:776–787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heintz AP, Odicino F, Maisonneuve P, Quinn MA, Benedet JL, Creasman WT, Ngan HY, Pecorelli S, Beller U (2006) Carcinoma of the ovary. FIGO 26th annual report on the results of treatment in Gynecological Cancer. Int J Gynaecol Obstet 95(Suppl 1):S161–S192

    Article  PubMed  Google Scholar 

  • Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M et al (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070

    Article  CAS  PubMed  Google Scholar 

  • Jayson GC, Kohn EC, Kitchener HC, Ledermann JA (2014) Ovarian cancer. Lancet 384:1376–1388

    Article  PubMed  Google Scholar 

  • Jia CM, Tian YY, Quan LN, Jiang L, Liu AC (2018) miR-26b-5p suppresses proliferation and promotes apoptosis in multiple myeloma cells by targeting JAG1. Pathol Res Pract 214:1388–1394

    Article  CAS  PubMed  Google Scholar 

  • Jiang J, Xie C, Liu Y, Shi Q, Chen Y (2018) Up-regulation of miR-383-5p suppresses proliferation and enhances chemosensitivity in ovarian cancer cells by targeting TRIM27. Biomed Pharmacother 109:595–601

    Article  CAS  PubMed  Google Scholar 

  • Lengyel E (2010) Ovarian cancer development and metastasis. Am J Pathol 177:1053–1064

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu GY, Gao ZH, Li L, Song TT, Sheng XG (2016) Expression of Jagged1 mRNA in human epithelial ovarian carcinoma tissues and effect of RNA interference of Jagged1 on growth of xenograft in nude mice. Zhonghua Fu Chan Ke Za Zhi 51:448–453

    CAS  PubMed  Google Scholar 

  • Liu J, Jiang Y, Wan Y, Zhou S, Thapa S, Cheng W (2018a) MicroRNA665 suppresses the growth and migration of ovarian cancer cells by targeting HOXA10. Mol Med Rep 18:2661–2668

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu XG, Xu J, Li F, Li MJ, Hu T (2018b) Down-regulation of miR-377 contributes to cisplatin resistance by targeting XIAP in osteosarcoma. Eur Rev Med Pharmacol Sci 22:1249–1257

    PubMed  Google Scholar 

  • Pearre DC, Tewari KS (2018) Targeted treatment of advanced ovarian cancer: spotlight on rucaparib. Ther Clin Risk Manag 14:2189–2201

    Article  PubMed  PubMed Central  Google Scholar 

  • Rastogi B, Kumar A, Raut SK, Panda NK, Rattan V, Joshi N, Khullar M (2017) Downregulation of miR-377 promotes oral squamous cell carcinoma growth and migration by targeting HDAC9. Cancer Invest 35:152–162

    Article  CAS  PubMed  Google Scholar 

  • Shen YH, Xie ZB, Yue AM, Wei QD, Zhao HF, Yin HD, Mai W, Zhong XG, Huang SR (2016) Expression level of microRNA-195 in the serum of patients with gastric cancer and its relationship with the clinicopathological staging of the cancer. Eur Rev Med Pharmacol Sci 20:1283–1287

    PubMed  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

    Article  PubMed  Google Scholar 

  • Wang CQ, Chen L, Dong CL, Song Y, Shen ZP, Shen WM, Wu XD (2017) MiR-377 suppresses cell proliferation and metastasis in gastric cancer via repressing the expression of VEGFA. Eur Rev Med Pharmacol Sci 21:5101–5111

    PubMed  Google Scholar 

  • Wu HH, Lin WC, Tsai KW (2014) Advances in molecular biomarkers for gastric cancer: miRNAs as emerging novel cancer markers. Expert Rev Mol Med 16:e1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye C, Hu Y, Wang J (2018) MicroRNA-377 targets zinc finger E-box-binding homeobox 2 to inhibit cell proliferation and invasion of cervical cancer. Oncol Res 27:183–192

    Article  PubMed  Google Scholar 

  • Zhang L, Volinia S, Bonome T, Calin GA, Greshock J, Yang N, Liu CG, Giannakakis A, Alexiou P, Hasegawa K et al (2008) Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer. Proc Natl Acad Sci USA 105:7004–7009

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhu L, Hou L, Ou J, Xu G, Jiang F, Hu C, Wang C (2019) MiR-199b represses porcine muscle satellite cells proliferation by targeting JAG1. Gene 691:24–33

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Bin Yang.

Ethics declarations

Conflict of interest

Liulin Tang, Bin Yang, Xiaolan Cao, Qin Li, Li Jiang and Dan Wang declare that they have no competing interests, and all authors should confirm its accuracy.

Ethical approval

The experimental protocol was obeyed by World Medical Association Declaration of Helsinki. Informed consent was obtained from all individual participants prior to the study.

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

Tang, L., Yang, B., Cao, X. et al. MicroRNA-377-3p inhibits growth and invasion through sponging JAG1 in ovarian cancer. Genes Genom 41, 919–926 (2019).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: