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MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7

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Tumor Biology

Abstract

MicroRNAs (miRNAs) are a class of small noncoding RNAs that play important roles in tumorigenesis and tumor progression through regulation of gene expression. Earlier, miR-142-3p was shown to decreased in cervical cancer cells; here; we explore the biological functional role of miR-142-3p and underlying mechanism in cervical cancer cells. We first detected the expression of miR-142-3p in six human cervical cancer cell lines and chose HeLa and SiHa cells for functional studies. By gain and loss of function experiments, we showed that overexpression of miR142-3p resulted in downregulation of Frizzled7 receptor (FZD7) and inhibited proliferation and invasion in HeLa and SiHa cells, whereas miR142-3p inhibitor-transfected cells showed reduced FZD7 expression and increased invasion capacity. In addition, we demonstrated that FZD7 was a direct target of miR-142-3p by dual luciferase assay and Western blot analysis. Overexpression of FZD7 expression was able to reverse the inhibitory effects induced by miR-142-3p. Taken together, miR-142-3p functions tumor suppressive effects in cell proliferation and invasion in cervical cancer cells, suggesting a potential therapeutic approach for cervical cancer.

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References

  1. Arbyn M, Castellsague X, de Sanjose S, Bruni L, Saraiya M, Bray F, et al. Worldwide burden of cervical cancer in 2008. Ann Oncol Off J Eur Soc Med Oncol/ESMO. 2011;22:2675–86.

    Article  CAS  Google Scholar 

  2. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer J Int Cancer. 2010;127:2893–917.

    Article  CAS  Google Scholar 

  3. Wang X, Tang S, Le SY, Lu R, Rader JS, Meyers C, et al. Aberrant expression of oncogenic and tumor-suppressive microRNAs in cervical cancer is required for cancer cell growth. PLoS ONE. 2008;3:e2557.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Duenas-Gonzalez A, Cetina L, Mariscal I, de la Garza J. Modern management of locally advanced cervical carcinoma. Cancer Treat Rev. 2003;29:389–99.

    Article  PubMed  Google Scholar 

  5. Glick SB, Clarke AR, Blanchard A, Whitaker AK. Cervical cancer screening, diagnosis and treatment interventions for racial and ethnic minorities: a systematic review. J Gen Intern Med. 2012;27:1016–32.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Reya T, Clevers H. Wnt signalling in stem cells and cancer. Nature. 2005;434:843–50.

    Article  CAS  PubMed  Google Scholar 

  7. Klaus A, Birchmeier W. Wnt signalling and its impact on development and cancer. Nat Rev Cancer. 2008;8:387–98.

    Article  CAS  PubMed  Google Scholar 

  8. Dissanayake SK, Wade M, Johnson CE, O’Connell MP, Leotlela PD, French AD, et al. The Wnt5a/protein kinase c pathway mediates motility in melanoma cells via the inhibition of metastasis suppressors and initiation of an epithelial to mesenchymal transition. J Biol Chem. 2007;282:17259–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Katoh M. WNT/PCP signaling pathway and human cancer (review). Oncol Rep. 2005;14:1583–8.

    CAS  PubMed  Google Scholar 

  10. Abu-Elmagd M, Garcia-Morales C, Wheeler GN. Frizzled7 mediates canonical Wnt signaling in neural crest induction. Dev Biol. 2006;298:285–98.

    Article  CAS  PubMed  Google Scholar 

  11. Asad M, Wong MK, Tan TZ, Choolani M, Low J, Mori S, et al. FZD7 drives in vitro aggressiveness in stem-a subtype of ovarian cancer via regulation of non-canonical Wnt/PCP pathway. Cell Death Dis. 2014;5:e1346.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kirikoshi H, Sekihara H, Katoh M. Up-regulation of frizzled-7 (FZD7) in human gastric cancer. Int J Oncol. 2001;19:111–5.

    CAS  PubMed  Google Scholar 

  13. Yang L, Wu X, Wang Y, Zhang K, Wu J, Yuan YC, et al. FZD7 has a critical role in cell proliferation in triple negative breast cancer. Oncogene. 2011;30:4437–46.

    Article  CAS  PubMed  Google Scholar 

  14. Merle P, Kim M, Herrmann M, Gupte A, Lefrancois L, Califano S, et al. Oncogenic role of the frizzled-7/beta-catenin pathway in hepatocellular carcinoma. J Hepatol. 2005;43:854–62.

    Article  CAS  PubMed  Google Scholar 

  15. King TD, Zhang W, Suto MJ, Li Y. Frizzled7 as an emerging target for cancer therapy. Cell Signal. 2012;24:846–51.

    Article  CAS  PubMed  Google Scholar 

  16. Nambotin SB, Lefrancois L, Sainsily X, Berthillon P, Kim M, Wands JR, et al. Pharmacological inhibition of frizzled-7 displays anti-tumor properties in hepatocellular carcinoma. J Hepatol. 2011;54:288–99.

    Article  CAS  PubMed  Google Scholar 

  17. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.

    Article  CAS  PubMed  Google Scholar 

  18. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  CAS  PubMed  Google Scholar 

  19. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by micrornas: are the answers in sight? Nat Rev Genet. 2008;9:102–14.

    Article  CAS  PubMed  Google Scholar 

  20. Croce CM, Calin GA. Mirnas, cancer, and stem cell division. Cell. 2005;122:6–7.

    Article  CAS  PubMed  Google Scholar 

  21. Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, et al. The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet. 2006;38:228–33.

    Article  CAS  PubMed  Google Scholar 

  22. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tang T, Wong HK, Gu W, Yu MY, To KF, Wang CC, et al. MicroRNA-182 plays an onco-miRNA role in cervical cancer. Gynecol Oncol. 2013;129:199–208.

    Article  CAS  PubMed  Google Scholar 

  24. Onder TT, Gupta PB, Mani SA, Yang J, Lander ES, Weinberg RA. Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res. 2008;68:3645–54.

    Article  CAS  PubMed  Google Scholar 

  25. Qureshi R, Arora H, Rizvi MA. EMT in cervical cancer: its role in tumour progression and response to therapy. Cancer Lett. 2015;356:321–31.

    Article  CAS  PubMed  Google Scholar 

  26. Deng B, Zhang S, Miao Y, Zhang Y, Wen F, Guo K. Down-regulation of frizzled-7 expression inhibits migration, invasion, and epithelial-mesenchymal transition of cervical cancer cell lines. Med Oncol. 2015;32:102.

    Article  PubMed  Google Scholar 

  27. Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005;7:719–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kent OA, Mendell JT. A small piece in the cancer puzzle: microRNAs as tumor suppressors and oncogenes. Oncogene. 2006;25:6188–96.

    Article  CAS  PubMed  Google Scholar 

  29. Wu L, Cai C, Wang X, Liu M, Li X, Tang H. MicroRNA-142-3p, a new regulator of RAC1, suppresses the migration and invasion of hepatocellular carcinoma cells. FEBS Lett. 2011;585:1322–30.

    Article  CAS  PubMed  Google Scholar 

  30. MacKenzie TN, Mujumdar N, Banerjee S, Sangwan V, Sarver A, Vickers S, et al. Triptolide induces the expression of miR-142-3p: a negative regulator of heat shock protein 70 and pancreatic cancer cell proliferation. Mol Cancer Ther. 2013;12:1266–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lv M, Zhang X, Jia H, Li D, Zhang B, Zhang H, et al. An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-alpha and cAMP/PKA pathways. Leukemia. 2012;26:769–77.

    Article  CAS  PubMed  Google Scholar 

  32. Lin RJ, Xiao DW, Liao LD, Chen T, Xie ZF, Huang WZ, et al. MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma. J Surg Oncol. 2012;105:175–82.

    Article  CAS  PubMed  Google Scholar 

  33. Shen WW, Zeng Z, Zhu WX, Fu GH. MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells. J Mol Med (Berl). 2013;91:989–1000.

    Article  CAS  Google Scholar 

  34. Yang YQ, Qi J, Xu JQ, Hao P. MicroRNA-142-3p, a novel target of tumor suppressor menin, inhibits osteosarcoma cell proliferation by down-regulation of FASN. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2014;35:10287–93.

    Article  CAS  Google Scholar 

  35. Barker N, Clevers H. Mining the Wnt pathway for cancer therapeutics. Nat Rev Drug Discov. 2006;5:997–1014.

    Article  CAS  PubMed  Google Scholar 

  36. Menezes ME. The Wnt/β-catenin signaling pathway in epithelial mesenchymal transition. J Postdoctoral Res. 2014;1:12.

    Google Scholar 

  37. Manzo-Merino J, Contreras-Paredes A, Vazquez-Ulloa E, Rocha-Zavaleta L, Fuentes-Gonzalez AM, Lizano M. The role of signaling pathways in cervical cancer and molecular therapeutic targets. Arch Med Res. 2014;45:525–39.

    Article  CAS  PubMed  Google Scholar 

  38. Carraro G, Shrestha A, Rostkovius J, Contreras A, Chao CM, El Agha E, et al. MiR-142-3p balances proliferation and differentiation of mesenchymal cells during lung development. Development. 2014;141:1272–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This study was supported by a grant from The First Affiliated Hospital of China Medical University (No. FSFH1214).

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Authors and Affiliations

  1. Department of Gynecology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, China

    Boya Deng, Yi Zhang, Fang Wen & Kejun Guo

  2. Central Laboratory, China Medical University, Shenyang, 110001, China

    Siyang Zhang

  3. Department of Pathology, The First Affiliated Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China

    Yuan Miao

Authors
  1. Boya Deng
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  2. Yi Zhang
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  3. Siyang Zhang
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  4. Fang Wen
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  5. Yuan Miao
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  6. Kejun Guo
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Correspondence to Boya Deng.

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Deng, B., Zhang, Y., Zhang, S. et al. MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7. Tumor Biol. 36, 8065–8073 (2015). https://doi.org/10.1007/s13277-015-3483-2

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  • DOI: https://doi.org/10.1007/s13277-015-3483-2

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