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MiR-21 Suppresses Anoikis through Targeting PDCD4 and PTEN in Human Esophageal Adenocarcinoma

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Summary

Anoikis is a form of apoptosis induced upon cell detachment from extracellular matrix. It has been determined that acquisition of resistance to anoikis is a critical step for tumor cell metastasis. MiR-21, the most prominent oncomiR, plays an important role in tumor progression. In this study, we revealed that up-regulation of miR-21 in human esophageal adenocarcinoma (EA) is associated with lymph node metastasis and poor survival rate. Because of the established anti-apoptosis effect of miR-21, it is tempting to speculate that miR-21 might contribute to tumor metastasis by regulating anoikis. qRT-PCR analysis demonstrated that miR-21 expression in OE33/AR cells (subpopulation of human EA OE33 cells that acquired resistance to anoikis) was significantly increased. Also, transfection of miR-21 mimics provided OE33 cells resisting to anoikis. By luciferase assays, we verified that PDCD4 and PTEN were the functional targets of miR-21. In mouse model, via tail vein injection experiment, we showed that the metastasis formation of OE33 cells in vivo could be mediated by changing the miR-21 expression pattern. Taken together, our findings suggested that miR-21 was involved in the regulation of anoikis in human EA cells. Targeting miR-21 may provide a novel strategy to prevent metastasis.

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References

  1. Paoli P, Giannoni E, Chiarugi P. Anoikis molecular pathways and its role in cancer progression. Biochim Biophys Acta, 2013,1833(12):3481–3498

    Article  PubMed  CAS  Google Scholar 

  2. Malagobadan S, Nagoor NH. Evaluation of MicroRNAs Regulating Anoikis Pathways and Its Therapeutic Potential. Biomed Res Int, 2015,2015:716816.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Yang J, Zheng Z, Yan X, et al. Integration of autophagy and anoikis resistance in solid tumors. Anat Rec (Hoboken), 2013,296(10):1501–1508

    Article  Google Scholar 

  4. Pachmayr E, Treese C, Stein U. Underlying Mechanisms for Distant Metastasis—Molecular Biology. Visc Med, 2017,33(1):11–20

    Article  PubMed  PubMed Central  Google Scholar 

  5. Slattum GM, Rosenblatt J. Tumour cell invasion: an emerging role for basal epithelial cell extrusion. Nat Rev Cancer, 2014,14(7):495–501

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet, 2011,12(12):861–874

    Article  PubMed  CAS  Google Scholar 

  7. Kong YW, Ferland-McCollough D, Jackson TJ, et al. microRNAs in cancer management. Lancet Oncol, 2012,13(6):e249–258

    Article  PubMed  CAS  Google Scholar 

  8. Gross N, Kropp J, Khatib H. MicroRNA Signaling in Embryo Development. Biology (Basel), 2017,6(3):34

    Google Scholar 

  9. Liu J, Zhu H, Yang X, et al. MicroRNA-21 is a novel promising target in cancer radiation therapy. Tumour Biol, 2014,35(5):3975–3979

    Article  PubMed  CAS  Google Scholar 

  10. Pfeffer SR, Yang CH, Pfeffer LM. The Role of miR-21 in Cancer. Drug Dev Res, 2015,76(6):270–277

    Article  PubMed  CAS  Google Scholar 

  11. Markou A, Zavridou M, Lianidou ES. miRNA-21 as a novel therapeutic target in lung cancer. Lung Cancer (Auckl), 2016,7:19–27

    CAS  Google Scholar 

  12. Zhao J, Schnitzler GR, Iyer LK, et al. MicroRNAOffset RNA Alters Gene Expression and Cell Proliferation. PLoS One, 2016,11(6):e0156772

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Zhu W, Xu B. MicroRNA-21 identified as predictor of cancer outcome: a meta-analysis. PLoS One, 2014,9(8):e103373

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Wang W, Li J, Zhu W, et al. MicroRNA-21 and the clinical outcomes of various carcinomas: a systematic review and meta-analysis. BMC Cancer, 2014,14:819

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Schafer ZT, Grassian AR, Song L, et al. Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature, 2009,461(7260):109–113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta DeltaC(T)) method. Methods, 2001,25(4):402–408

    Article  PubMed  CAS  Google Scholar 

  17. Yu SJ, Hu JY, Kuang XY, et al. MircroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer. Clin Cancer Res, 2013,19(6):1389–1399

    Article  PubMed  CAS  Google Scholar 

  18. Wu MF, Yang J, Xiang T, et al. miR-21 targets Fas ligand-mediated apoptosis in breast cancer cell line MCF-7. J Huazhong Univ Sci Technolog Med Sci, 2014,34(2):190–194

    Article  PubMed  CAS  Google Scholar 

  19. Feber A, Xi L, Luketich JD, et al. MicroRNA expression profiles of esophageal cancer. J Thorac Cardiovasc Surg, 2008,135(2):255–260

    Article  PubMed  CAS  Google Scholar 

  20. Meng XR, Lu P, Mei JZ, et al. Expression analysis of miRNA and target mRNAs in esophageal cancer. Braz J Med Biol Res, 2014,47(9):811–817

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Winther M, Alsner J, Tramm T, et al. Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer. Acta Oncol, 2015,54(9):1582–1591

    Article  PubMed  CAS  Google Scholar 

  22. Pan X, Wang ZX, Wang R. MicroRNA-21: a novel therapeutic target in human cancer. Cancer Biol Ther, 2010,10(12):1224–1232

    Article  PubMed  CAS  Google Scholar 

  23. Young MR, Santhanam AN, Yoshikawa N, et al. Have tumor suppressor PDCD4 and its counteragent oncogenic miR-21 gone rogue? Mol Interv, 2010,10(2):76–79

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Wang G, Wang JJ, Tang HM, et al. Targeting strategies on miRNA-21 and PDCD4 for glioblastoma. Arch Biochem Biophys, 2015,580:64–74

    Article  PubMed  CAS  Google Scholar 

  25. Ming M, He YY. PTEN in DNA damage repair. Cancer Lett, 2012,319(2):125–129

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Khalid A, Hussain T, Manzoor S, et al. PTEN: A potential prognostic marker in virus-induced hepatocellular carcinoma. Tumour Biol, 2017,39(6):1010428317705754

    Article  PubMed  Google Scholar 

  27. Kumar A, Rajendran V, Sethumadhavan R, et al. AKT kinase pathway: a leading target in cancer research. Sci World J, 2013,2013:756134

    Google Scholar 

  28. Chen J, Xu T, Chen C. The critical roles of miR-21 in anti-cancer effects of curcumin. Ann Transl Med, 2015,3(21):330

    PubMed  PubMed Central  Google Scholar 

  29. Gaudelot K, Gibier JB, Pottier N, et al. Targeting miR-21 decreases expression of multi-drug resistant genes and promotes chemosensitivity of renal carcinoma. Tumour Biol, 2017,39(7):1010428317707372

    Article  PubMed  Google Scholar 

  30. He C, Dong X, Zhai B, et al. MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Oncotarget, 2015,6(30):28867–28881

    PubMed  PubMed Central  Google Scholar 

  31. Yan LX, Wu QN, Zhang Y, et al. Knockdown of miR-21 in human breast cancer cell lines inhibits proliferation, in vitro migration and in vivo tumor growth. Breast Cancer Res, 2011,13(1):R2

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Sicard F, Gayral M, Lulka H, et al. Targeting miR-21 for the therapy of pancreatic cancer. Mol Ther, 2013,21(5):986–994

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Meng-ya Zhao

  2. Department of Medical Ultrasound, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430060, China

    La-mei Wang

  3. Department of Emergency Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Jing Liu

  4. Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China

    Xing Huang, Jing Liu & Ya-fei Zhang

Authors
  1. Meng-ya Zhao
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  2. La-mei Wang
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  3. Jing Liu
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  4. Xing Huang
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  5. Jing Liu
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  6. Ya-fei Zhang
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Corresponding author

Correspondence to Ya-fei Zhang.

Additional information

This project was supported by grants from the National Natural Science Foundation of China (No. 81470818, No. 81472735 and No. 81472033).

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Zhao, My., Wang, Lm., Liu, J. et al. MiR-21 Suppresses Anoikis through Targeting PDCD4 and PTEN in Human Esophageal Adenocarcinoma. CURR MED SCI 38, 245–251 (2018). https://doi.org/10.1007/s11596-018-1872-7

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  • DOI: https://doi.org/10.1007/s11596-018-1872-7

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