Skip to main content

Advertisement

SpringerLink
Log in

RETRACTED ARTICLE: miR-494 suppresses tumor growth of epithelial ovarian carcinoma by targeting IGF1R

  • Original Article
  • Published:
Tumor Biology

21 December 2021 This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.3233/TUB-219010

Abstract

A growing body of evidence suggests that microRNA-494 (miR-494) could act as tumor-suppressive or oncogenic microRNAs (miRNAs) in different types of tumors. However, the biological roles and underlying mechanisms of miR-494 remain unknown in human epithelial ovarian carcinoma (EOC). Therefore, the aims of this study were to investigate the miR-494 expression and the significance of its clinical diagnosis in patients suffering EOC and to analyze its role and underlying molecular mechanism on the carcinogenesis of EOC. Here, we found that miR-494 was significantly decreased in EOC cell lines and tissues and its expression was negatively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, high pathological grade, and lymph node metastasis (all P < 0.01). Functional studies showed that overexpression of miR-494 in EOC cells could remarkably inhibit proliferation, colony formation, migration, and invasion and induce cell apoptosis, G0/G1 phase arrest. An in vivo analysis revealed that the overexpression of miR-494 suppressed tumor growth in a nude mouse xenograft model system. Bioinformatic assay and dual-luciferase assay confirmed that insulin-like growth factor 1 receptor (IGF1R) was as a direct target of miR-494 in EOC cells. Western blot assay showed that overexpression of miR-494 inhibited IGF1R expression and its downstream signal protein expression. In addition, downregulation of IGF1R has similar effects with miR-494 overexpression on EOC cells and overexpression of IGF1R effectively rescued the inhibition of overexpressed miR-494 in EOC cells. These data suggested that miR-494 functions as a tumor suppressor in EOC by targeting IGF1R.

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

Change history

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63:11–30.

    Article  PubMed  Google Scholar 

  2. Permuth-Wey J, Sellers TA. Epidemiology of ovarian cancer. Methods Mol Biol. 2009;472:413–37.

    Article  PubMed  Google Scholar 

  3. Legge F, Ferrandina G, Salutari V, Scambia G. Biological characterization of ovarian cancer: prognostic and therapeutic implications. Ann Oncol. 2005;16:95–101.

    Article  Google Scholar 

  4. Coleman RL, Monk BJ, Sood AK, Herzog TJ. Latest research and treatment of advanced-stage epithelial ovarian cancer. Nat Rev Clin Oncol. 2013;10:211–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Miska EA. How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 2005;15:563.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM. Bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell. 2003;113:25–36.

    Article  CAS  PubMed  Google Scholar 

  8. Sun K, Lai EC. Adult-specific functions of animal microRNAs. Nat Rev Genet. 2013;14:535–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Seton-Rogers S. Tumour suppressors: Hippo promotes microRNA processing. Nat Rev Cancer. 2014;14:216–7.

    PubMed  Google Scholar 

  10. Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang X, Han C, He J: Research progress of oncogene and tumor suppressor gene in bladder cancer. Panminerva Med. 2015 (in press).

  12. Diakos C, Zhong S, Xiao Y, Zhou M, Vasconcelos GM, Krapf G, et al. TEL-AML1 regulation of survivin and apoptosis via miRNA-494 and miRNA-320a. Blood. 2010;116:4885–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Duan H, Jiang Y, Zhang H, Wu Y. MiR-320 and miR-494 affect cell cycles of primary murine bronchial epithelial cells exposed to benzo[a]pyrene. Toxicol In Vitro. 2010;24:928–35.

    Article  CAS  PubMed  Google Scholar 

  14. Zhao JJ, Yang J, Lin J, Yao N, Zhu Y, Zheng J, et al. Identification of miRNAs associated with tumorigenesis of retinoblastoma by miRNA microarray analysis. Childs Nerv Syst. 2009;25:13–20.

    Article  PubMed  Google Scholar 

  15. Liu K, Liu S, Zhang W, Jia B, Tan L, Jin Z, et al. miR-494 promotes cell proliferation, migration and invasion, and increased sorafenib resistance in hepatocellular carcinoma by targeting PTEN. Oncol Rep. 2015;34:1003–10.

    Article  CAS  PubMed  Google Scholar 

  16. Lim L, Balakrishnan A, Huskey N, Jones KD, Jodari M, Ng R, et al. MicroRNA-494 within an oncogenic microRNA megacluster regulates G1/S transition in liver tumorigenesis through suppression of mutated in colorectal cancer. Hepatology. 2014;59:202–15.

    Article  CAS  PubMed  Google Scholar 

  17. Liu Y, Li X, Zhu S, Zhang JG, Yang M, Qin Q, et al. Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc. Gene Ther. 2015;22:729–38.

    Article  CAS  PubMed  Google Scholar 

  18. Shen PF, Chen XQ, Liao YC, Chen N, Zhou Q, Wei Q, et al. MicroRNA-494-3p targets CXCR4 to suppress the proliferation, invasion, and migration of prostate cancer. Prostate. 2014;74:756–67.

    Article  CAS  PubMed  Google Scholar 

  19. Romano G, Acunzo M, Garofalo M, Di Leva G, Cascione L, Zanca C, et al. MiR-494 is regulated by ERK1/2 and modulates trail-induced apoptosis in non-small-cell lung cancer through BIM down-regulation. Proc Natl Acad Sci U S A. 2012;109:16570–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kim WK, Park M, Kim YK, Tae YK, Yang HK, Lee JM, et al. MicroRNA-494 downregulates kit and inhibits gastrointestinal stromal tumor cell proliferation. Clin Cancer Res. 2011;17:7584–94.

    Article  CAS  PubMed  Google Scholar 

  21. Yamanaka S, Campbell NR, An F, Kuo SC, Potter JJ, Mezey E, et al. Coordinated effects of microRNA-494 induce G2/M arrest in human cholangiocarcinoma. Cell Cycle. 2012;11:2729–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kim YW, Kim EY, Jeon D, Liu JL, Kim HS, Choi JW, et al. Differential microRNA expression signatures and cell type-specific association with taxol resistance in ovarian cancer cells. Drug Des Devel Ther. 2014;8:293–314.

    PubMed  PubMed Central  Google Scholar 

  23. Sanabria-Figueroa E, Donnelly SM, Foy KC, Buss MC, Castellino RC, Paplomata E, et al. Insulin-like growth factor-1 receptor signaling increases the invasive potential of human epidermal growth factor receptor 2-overexpressing breast cancer cells via Src-focal adhesion kinase and forkhead box protein M1. Mol Pharmacol. 2015;87:150–61.

    Article  PubMed  PubMed Central  Google Scholar 

  24. King SM, Modi DA, Eddie SL, Burdette JE. Insulin and insulin-like growth factor signaling increases proliferation and hyperplasia of the ovarian surface epithelium and decreases follicular integrity through upregulation of the PI3-kinase pathway. J Ovarian Res. 2013;6:12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Osaki LH, Gama P. MAPKs and signal transduction in the control of gastrointestinal epithelial cell proliferation and differentiation. Int J Mol Sci. 2013;14:10143–61.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Cao Z, Liu LZ, Dixon DA, Zheng JZ, Chandran B, Jiang BH. Insulin-like growth factor-I induces cyclooxygenase-2 expression via PI3K, MAPK and PKC signaling pathways in human ovarian cancer cells. Cell Signal. 2007;19:1542–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Gest C, Mirshahi P, Li H, Pritchard LL, Joimel U, Blot E, et al. Ovarian cancer: Stat3, RhoA and IGF-IR as therapeutic targets. Cancer Lett. 2012;317:207–17.

    Article  CAS  PubMed  Google Scholar 

  28. Gotlieb WH, Bruchim I, Gu J, Shi Y, Camirand A, Blouin MJ, et al. Insulin-like growth factor receptor I targeting in epithelial ovarian cancer. Gynecol Oncol. 2006;100:389–96.

    Article  CAS  PubMed  Google Scholar 

  29. Coppola D, Saunders B, Fu L, Mao W, Nicosia SV. The insulin-like growth factor 1 receptor induces transformation and tumorigenicity of ovarian mesothelial cells and down-regulates their Fas-receptor expression. Cancer Res. 1999;59:3264–70.

    CAS  PubMed  Google Scholar 

  30. Xue M, Cao X, Zhong Y, Kuang D, Liu X, Zhao Z, et al. Insulin-like growth factor-1 receptor (IGF1R) kinase inhibitors in cancer therapy: advances and perspectives. Curr Pharm Des. 2012;18:2901–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Author notes

    Authors and Affiliations

    1. Department of Obstetrics and Gynecology, The First Hospital of Jilin University, Changchun, 130021, Jilin Province, China

      Na Li, Xiaosu Zhao, Shi Zhang & Jin He

    2. Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, 130041, Jilin Province, China

      Lufei Wang & Manhua Cui

    Authors
    1. Na Li
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Xiaosu Zhao
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Lufei Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Shi Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Manhua Cui
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Jin He
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Manhua Cui or Jin He.

    Ethics declarations

    Conflicts of interest

    None

    Additional information

    This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.3233/TUB-219010

    Manhua Cui and Jin He contributed equally to this work.

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Li, N., Zhao, X., Wang, L. et al. RETRACTED ARTICLE: miR-494 suppresses tumor growth of epithelial ovarian carcinoma by targeting IGF1R. Tumor Biol. 37, 7767–7776 (2016). https://doi.org/10.1007/s13277-015-4603-8

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-015-4603-8

    Keyword

    Search

    Navigation