Skip to main content

Advertisement

Log in

Upregulation of miR-197 inhibits cell proliferation by directly targeting IGFBP5 in human uterine leiomyoma cells

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Uterine leiomyoma (ULM), one of the most common reproductive tract neoplasms in premenopausal women, is a kind of benign tumor with multigene involved. Finding and studying the key gene involved has been a long-needed factor for developing non-surgery therapy and prevention methods. The dysregulated microRNAs were reported to play important roles in ULM pathobiology by regulating tumor growth. Our investigations have revealed that miR-197 is at low expression in ULM. Characterization of the effects of miR-197 in ULM demonstrated that downregulation of miR-197 increased cell growth and induced cell cycle arrest in the G0/G1 phase in vitro, while upregulation of miR-197 expression had the opposite effect on ULM growth and progression. Further research on the mechanism of miR-197 on the proliferation of ULM cells, we showed that miR-197 inhibited cell proliferation of ULM by directly targeting IGFBP5, which was overexpressed in ULM and played an important role in the etiology of ULM. These findings obtained in this study deliver insights and further expand our understanding of the role of miR-197 and its target IGFBP5 in ULM development, which provides a potential novel therapeutic agent to target the proliferation of ULM cells.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Chivukula RR, Shi G, Acharya A, Mills EW, Zeitels LR, Anandam JL, Abdelnaby AA, Balch GC, Mansour JC, Yopp AC, Maitra A, Mendell JT (2014) An essential mesenchymal function for miR-143/145 in intestinal epithelial regeneration. Cell 157(5):1104–1116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cirilo PD, Marchi FA, Barros Filho M d C, Rocha RM, Domingues MA, Jurisica I, Pontes A, Rogatto SR (2013) An integrative genomic and transcriptomic analysis reveals potential targets associated with cell proliferation in uterine leiomyomas. PLoS One 8(3):e57901

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dai W, Wang C, Wang F, Wang Y, Shen M, Chen K, Cheng P, Zhang Y, Yang J, Zhu R, Zhang H, Li J, Zheng Y, Lu J, Zhou Y, Xu L, Guo C (2014) Anti-miR-197 inhibits migration in HCC cells by targeting KAI 1/CD82. Biochem Biophys Res Commun 446(2):541–548

    Article  CAS  PubMed  Google Scholar 

  • Du L, Schageman JJ, Subauste MC, Saber B, Hammond SM, Prudkin L, Wistuba II, Ji L, Roth JA, Minna JD, Pertsemlidis A (2009) miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS. Mol Cancer Res 7(8):1234–1243

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Feng Y, Zhao X, Zhou C, Yang L, Liu Y, Bian C, Gou J, Lin X, Wang Z, Zhao X (2013) The associations between the Val158Met in the catechol-O-methyltransferase (COMT) gene and the risk of uterine leiomyoma (ULM). Gene 529(2):296–299

    Article  CAS  PubMed  Google Scholar 

  • Güllü G, Karabulut S, Akkiprik M (2012) Functional roles and clinical values of insulin-like growth factor-binding protein-5 in different types of cancers. Chin J Cancer 31(6):266–280

    Article  PubMed Central  PubMed  Google Scholar 

  • Hamada S, Satoh K, Miura S, Hirota M, Kanno A, Masamune A, Kikuta K, Kume K, Unno J, Egawa S, Motoi F, Unno M, Shimosegawa T (2013) miR-197 induces epithelial-mesenchymal transition in pancreatic cancer cells by targeting p120 catenin. J Cell Physiol 228(6):1255–1263

    Article  CAS  PubMed  Google Scholar 

  • Huang JT, Wang J, Srivastava V, Sen S, Liu SM (2014) MicroRNA machinery genes as novel biomarkers for cancer. Front Oncol 4:113

    PubMed Central  PubMed  Google Scholar 

  • Kim KM, Lim SK (2014) Role of miRNAs in bone and their potential as therapeutic targets. Curr Opin Pharmacol 16C:133–141

    Article  Google Scholar 

  • Lee DH, Kim JE, Kang YJ (2013) Insulin like growth factor binding protein-5 regulates excessive vascular smooth muscle cell proliferation in spontaneously hypertensive rats via ERK 1/2 phosphorylation. Korean J Physiol Pharmacol 17(2):157–162

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lehmann U, Streichert T, Otto B, Albat C, Hasemeier B, Christgen H, Schipper E, Hille U, Kreipe HH, Länger F (2010) Identification of differentially expressed microRNAs in human male breast cancer. BMC Cancer 10:109

    Article  PubMed Central  PubMed  Google Scholar 

  • Li X, Zhang Y, Zhang H, Liu X, Gong T, Li M, Sun L, Ji G, Shi Y, Han Z, Han S, Nie Y, Chen X, Zhao Q, Ding J, Wu K, Daiming F (2011) miRNA-223 promotes gastric cancer invasion and metastasis by targeting tumor suppressor EPB41L3. Mol Cancer Res 9:824–833

    Article  CAS  PubMed  Google Scholar 

  • Liang PI, Wang YH, Wu TF, Wu WR, Liao AC, Shen KH, Hsing CH, Shiue YL, Huang HY, Hsu HP, Chen LT, Lin CY, Tai C, Wu JY, Li CF (2013) IGFBP-5 overexpression as a poor prognostic factor in patients with urothelial carcinomas of upper urinary tracts and urinary bladder. J Clin Pathol 66(7):573–582

    Article  CAS  PubMed  Google Scholar 

  • Nam JW, Rissland OS, Koppstein D, Abreu-Goodger C, Jan CH, Agarwal V, Yildirim MA, Rodriguez A, Bartel DP (2014) Global analyses of the effect of different cellular contexts on microRNA targeting. Mol Cell 53(6):1031–1043

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Qiang W, Liu Z, Serna VA, Druschitz SA, Liu Y, Espona-Fiedler M, Wei JJ, Kurita T (2014) Down-regulation of miR-29b is essential for pathogenesis of uterine leiomyoma. Endocrinology 155(3):663–669

    Article  PubMed Central  PubMed  Google Scholar 

  • Simon S, Grabellus F, Ferrera L, Galietta L, Schwindenhammer B, Mühlenberg T, Taeger G, Eilers G, Treckmann J, Breitenbuecher F, Schuler M, Taguchi T, Fletcher JA, Bauer S (2013) DOG1 regulates growth and IGFBP5 in gastrointestinal stromal tumors. Cancer Res 73(12):3661–3670

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Wang T, Zhang X, Obijuru L, Laser J, Aris V, Lee P, Mittal K, Soteropoulos P, Wei JJ (2007) A micro-RNA signature associated with race, tumor size, and target gene activity in human uterine leiomyomas. Genes Chromosom Cancer 46(4):336–347

    Article  CAS  PubMed  Google Scholar 

  • Wong TS, Liu XB, Wong BY, Ng RW, Yuen AP, Wei WI (2008) Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin Cancer Res 14:2588–2592

    Article  CAS  PubMed  Google Scholar 

  • Zheng D, Haddadin S, Wang Y, Gu LQ, Perry MC, Freter CE, Wang MX (2011) Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int J Clin Exp Pathol 4(6):575–586

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jie Tan.

Additional information

Editor: T. Okamoto

Jing Ling and Li Jiang contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ling, J., Jiang, L., Zhang, C. et al. Upregulation of miR-197 inhibits cell proliferation by directly targeting IGFBP5 in human uterine leiomyoma cells. In Vitro Cell.Dev.Biol.-Animal 51, 835–842 (2015). https://doi.org/10.1007/s11626-015-9887-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-015-9887-x

Keywords

Navigation