Tumor Biology

, Volume 36, Issue 3, pp 1913–1921 | Cite as

MiR-492 contributes to cell proliferation and cell cycle of human breast cancer cells by suppressing SOX7 expression

Research Article

Abstract

MicroRNAs (miRNAs) have emerged as important regulators that potentially play critical roles in cancer cell biological processes. Previous studies have shown that miR-492 plays an important role in cell tumorigenesis in multiple kinds of human cancer cells. However, the underlying mechanisms of this microRNA in breast cancer remain largely unknown. In the present study, we investigated miR-492’s role in cell proliferation of breast cancer. MiR-492 expression was markedly upregulated in breast cancer tissues and breast cancer cells. Overexpression of miR-492 promoted the proliferation and anchorage-independent growth of breast cancer cells. Bioinformatics analysis further revealed sex-determining region Y-box 7 (SOX7), a putative tumor suppressor, as a potential target of miR-492. Data from luciferase reporter assays showed that miR-492 directly binds to the 3′-untranslated region (3′-UTR) of SOX7 messenger RNA (mRNA) and repressed expression at both transcriptional and translational levels. Ectopic expression of miR-492 led to downregulation of SOX7 protein, which resulted in the upregulation of cyclin D1 and c-Myc. In functional assays, SOX7 silenced in miR-492-in-transfected ZR-75-30 cells has positive effect to promote cell proliferation, suggesting that direct SOX7 downregulation is required for miR-492-induced cell proliferation and cell cycle of breast cancer. In sum, these results suggest that miR-492 represents a potential onco-miR and participates in breast cancer carcinogenesis by suppressing SOX7 expression.

Keywords

MiR-492 Breast cancer SOX7 Cell proliferation Cell cycle 

Notes

Acknowledgments

This work was supported by the Department of General Surgery, Guangzhou First People’s Hospital, Guangzhou Medical University. The study was supported by the Guangdong Provincial Science & Technology Projects (2013B021800041). All the authors designed the study together, performed the experiment together, analyzed the data, and wrote the paper; all the authors approved the final manuscript.

Conflicts of interest

None

References

  1. 1.
    Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  2. 2.
    Dalmay T. Mechanism of miRNA-mediated repression of mRNA translation. Essays Biochem. 2013;54:29–38.CrossRefPubMedGoogle Scholar
  3. 3.
    van Kouwenhove M, Kedde M, Agami R. MicroRNA regulation by RNA-binding proteins and its implications for cancer. Nat Rev Cancer. 2011;11:644–56.CrossRefPubMedGoogle Scholar
  4. 4.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.CrossRefPubMedGoogle Scholar
  5. 5.
    Li P, Xie XB, Chen Q, Pang GL, Luo W, Tu JC, et al. MiRNA-15a mediates cell cycle arrest and potentiates apoptosis in breast cancer cells by targeting synuclein-gamma. Asian Pac J Cancer Prev: APJCP. 2014;15:6949–54.CrossRefPubMedGoogle Scholar
  6. 6.
    Krutilina R, Sun W, Sethuraman A, Brown M, Seagroves TN, Pfeffer LM, et al. MicroRNA-18a inhibits hypoxia-inducible factor 1-alpha activity and lung metastasis in basal breast cancers. Breast Cancer Res. 2014;16:R78.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Paulmurugan R. MicroRNAs—a new generation molecular targets for treating cellular diseases. Theranostics. 2013;3:927–9.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Zhang W, Liu J, Wang G. The role of microRNAs in human breast cancer progression. Tumour Biol J Int Soc Oncodev Biol Med. 2014;35:6235–44.CrossRefGoogle Scholar
  9. 9.
    von Frowein J, Pagel P, Kappler R, von Schweinitz D, Roscher A. MicroRNA-492 is processed from the keratin 19 gene and up-regulated in metastatic hepatoblastoma. Hepatology (Baltimore, Md). 2011;53:833–42.CrossRefGoogle Scholar
  10. 10.
    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: ChNS: Off J Int Soc Pediatr Neurosurg. 2009;25:13–20.CrossRefGoogle Scholar
  11. 11.
    Hui AB, Lin A, Xu W, Waldron L, Perez-Ordonez B, Weinreb I, et al. Potentially prognostic miRNAs in HPV-associated oropharyngeal carcinoma. Clin Cancer Res: Off J Am Assoc Cancer Res. 2013;19:2154–62.CrossRefGoogle Scholar
  12. 12.
    Wu GG, Li WH, He WG, Jiang N, Zhang GX, Chen W, et al. MiR-184 post-transcriptionally regulates SOX7 expression and promotes cell proliferation in human hepatocellular carcinoma. PLoS One. 2014;9:e88796.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Chan DW, Mak CS, Leung TH, Chan KK, Ngan HY. Down-regulation of SOX7 is associated with aberrant activation of Wnt/β-catenin signaling in endometrial cancer. Oncotarget. 2012;3:1546–56.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Zhang Y, Huang S, Dong W, Li L, Feng Y, Pan L, et al. SOX7, down-regulated in colorectal cancer, induces apoptosis and inhibits proliferation of colorectal cancer cells. Cancer Lett. 2009;277:29–37.CrossRefPubMedGoogle Scholar
  15. 15.
    Rajabi HN, Takahashi C, Ewen ME. Retinoblastoma protein and MyoD function together to effect the repression of fra-1 and in turn cyclin D1 during terminal cell cycle arrest associated with myogenesis. J Biol Chem. 2014;289:23417–27.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Cui J, Xi H, Cai A, Bian S, Wei B, Chen L. Decreased expression of SOX7 correlates with the upregulation of the Wnt/beta-catenin signaling pathway and the poor survival of gastric cancer patients. Int J Mol Med. 2014;34:197–204.PubMedGoogle Scholar
  17. 17.
    Stovall DB, Wan M, Miller LD, Cao P, Maglic D, Zhang Q, et al. The regulation of SOX7 and its tumor suppressive role in breast cancer. Am J Pathol. 2013;183:1645–53.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Stovall DB, Cao P, Sui G. SOX7: from a developmental regulator to an emerging tumor suppressor. Histol Histopathol. 2014;29:439–45.PubMedGoogle Scholar
  19. 19.
    He M, Li Y, Zhang L, Li L, Shen Y, Lin L, et al. Curcumin suppresses cell proliferation through inhibition of the Wnt/beta-catenin signaling pathway in medulloblastoma. Oncol Rep. 2014;32:173–80.PubMedGoogle Scholar
  20. 20.
    Zhi X, Tao J, Xie K, Zhu Y, Li Z, Tang J, et al. Muc4-induced nuclear translocation of beta-catenin: a novel mechanism for growth, metastasis and angiogenesis in pancreatic cancer. Cancer Lett. 2014;346:104–13.CrossRefPubMedGoogle Scholar
  21. 21.
    Lee MA, Park HJ, Chung HJ, Kim WK, Lee SK. Antitumor activity of 2-hydroxycinnamaldehyde for human colon cancer cells through suppression of beta-catenin signaling. J Nat Prod. 2013;76:1278–84.CrossRefPubMedGoogle Scholar
  22. 22.
    Arabi A, Wu S, Ridderstrale K, Bierhoff H, Shiue C, Fatyol K, et al. c-Myc associates with ribosomal DNA and activates RNA polymerase i transcription. Nat Cell Biol. 2005;7:303–10.CrossRefPubMedGoogle Scholar
  23. 23.
    Grewal SS, Li L, Orian A, Eisenman RN, Edgar BA. Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development. Nat Cell Biol. 2005;7:295–302.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of General Surgery, Guangzhou First People’s HospitalGuangzhou Medical UniversityGuangzhouPeople’s Republic of China

Personalised recommendations