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RETRACTED ARTICLE: shRNA-Mediated EMMPRIN Silencing Inhibits Human Leukemic Monocyte Lymphoma U937 Cell Proliferation and Increases Chemosensitivity to Adriamycin

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This article was retracted on 15 January 2022

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Abstract

EMMPRIN is a widely distributed cell surface glycoprotein, which plays an important role in tumor progression and confers resistance to some chemotherapeutic drugs. Recent studies have shown that EMMPRIN overexpression indicates poor prognosis in acute myeloid leukemia (AML). However, little was known on the role of EMMPRIN in leukemia. Human leukemia cell line U937 was stably transfected with a EMMPRIN-targeted shRNA-containing vector to investigate the effect of EMMPRIN on cellular functions. EMMPRIN expression was monitored by qRT-PCR and Western blotting. Cell viability and proliferation were determined by trypan blue exclusion and BrdU labeling, respectively. Cell cycle and apoptosis were analyzed by flow cytometry. Cytotoxicity of chemotherapeutic agent adriamycin on cells was assessed by MTT assay. Knockdown of EMMPRIN gene significantly inhibited cell viability and decreased cell proliferation. Fluorescence-activated cell-sorting analysis revealed that the reduced EMMPRIN expression resulted in cell cycle arrest at G1 phase and induced apoptosis. Meanwhile, western blotting analysis showed that EMMPRIN knockdown was associated with downregulation of cell cycle- and apoptosis-related molecules including cyclin D1, cyclin E, as well as increase in cleavage of caspase-3 and PARP. This study also showed that silencing of EMMPRIN sensitized U937 cells to Adriamycin. EMMPRIN is involved in proliferation, growth, and chemosensitivity of human AML line U937, indicating that EMMPRIN may be a promising therapeutic target for AML.

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References

  1. Estey, E., & Dohner, H. (2006). Acute myeloid leukaemia. Lancet, 368(9550), 1894–1907.

    Article  Google Scholar 

  2. Smith, M., et al. (2004). Adult acute myeloid leukaemia. Critical Reviews in Oncology Hematology, 50(3), 197–222.

    Article  Google Scholar 

  3. Groschel, S., et al. (2010). High EVI1 expression predicts outcome in younger adult patients with acute myeloid leukemia and is associated with distinct cytogenetic abnormalities. Journal of Clinical Oncology, 28(12), 2101–2107.

    Article  Google Scholar 

  4. Stirewalt, D. L., Meshinchi, S., & Radich, J. P. (2003). Molecular targets in acute myelogenous leukemia. Blood Reviews, 17(1), 15–23.

    Article  Google Scholar 

  5. Smith, M. L., Hills, R. K., & Grimwade, D. (2011). Independent prognostic variables in acute myeloid leukaemia. Blood Reviews, 25(1), 39–51.

    Article  CAS  Google Scholar 

  6. Meijer, E., & Cornelissen, J. J. (2008). Allogeneic stem cell transplantation in acute myeloid leukemia in first or subsequent remission: Weighing prognostic markers predicting relapse and risk factors for non-relapse mortality. Seminars in Oncology, 35(4), 449–457.

    Article  CAS  Google Scholar 

  7. Schmid, C., & Kolb, H. J. (2007). Allogeneic stem cell transplantation in the management of acute myeloid leukemia. Medizinische Klinik (Munich), 102(4), 317–323.

    Article  CAS  Google Scholar 

  8. Zhou, F. L., et al. (2010). Involvement of oxidative stress in the relapse of acute myeloid leukemia. Journal of Biological Chemistry, 285(20), 15010–15015.

    Article  CAS  Google Scholar 

  9. Fiedler, W., et al. (2001). Role of angiogenesis inhibitors in acute myeloid leukemia. Cancer Journal, 7(Suppl 3), S129–S133.

    Google Scholar 

  10. Fu, J., et al. (2010). CD147 and VEGF co-expression predicts prognosis in patients with acute myeloid leukemia. Japanese Journal of Clinical Oncology, 40(11), 1046–1052.

    Article  Google Scholar 

  11. Ranuncolo, S. M., et al. (2003). Plasma MMP-9 (92 kDa-MMP) activity is useful in the follow-up and in the assessment of prognosis in breast cancer patients. International Journal of Cancer, 106(5), 745–751.

    Article  CAS  Google Scholar 

  12. Jin, J. S., et al. (2006). Increasing expression of extracellular matrix metalloprotease inducer in ovary tumors: tissue microarray analysis of immunostaining score with clinicopathological parameters. International Journal of Gynecological Pathology, 25(2), 140–146.

    Article  Google Scholar 

  13. Sameshima, T., et al. (2000). Expression of emmprin (CD147), a cell surface inducer of matrix metalloproteinases, in normal human brain and gliomas. International Journal of Cancer, 88(1), 21–27.

    Article  CAS  Google Scholar 

  14. Zheng, H. C., et al. (2006). Upregulated EMMPRIN/CD147 might contribute to growth and angiogenesis of gastric carcinoma: a good marker for local invasion and prognosis. British Journal of Cancer, 95(10), 1371–1378.

    Article  CAS  Google Scholar 

  15. Bordador, L. C., et al. (2000). Expression of emmprin by oral squamous cell carcinoma. International Journal of Cancer, 85(3), 347–352.

    Article  CAS  Google Scholar 

  16. Kanekura, T., Chen, X., & Kanzaki, T. (2002). Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts. International Journal of Cancer, 99(4), 520–528.

    Article  CAS  Google Scholar 

  17. Li, Y., et al. (2009). HAb18G (CD147), a cancer-associated biomarker and its role in cancer detection. Histopathology, 54(6), 677–687.

    Article  CAS  Google Scholar 

  18. Zhang, Q., et al. (2007). Expression of CD147 as a significantly unfavorable prognostic factor in hepatocellular carcinoma. European Journal of Cancer Prevention, 16(3), 196–202.

    Article  Google Scholar 

  19. Tan, H., et al. (2008). CD147 expression as a significant prognostic factor in differentiated thyroid carcinoma. Transl Res, 152(3), 143–149.

    Article  CAS  Google Scholar 

  20. Sato, M., et al. (2013). EMMPRIN promotes angiogenesis, proliferation, invasion and resistance to sunitinib in renal cell carcinoma, and its level predicts patient outcome. PLoS One, 8(9), e74313.

    Article  CAS  Google Scholar 

  21. Wang, B., et al. (2010). RNAi-mediated silencing of CD147 inhibits tumor cell proliferation, invasion and increases chemosensitivity to cisplatin in SGC7901 cells in vitro. J Exp Clin Cancer Res, 29, 61.

    Article  Google Scholar 

  22. Yang, J. M., et al. (2003). Overexpression of extracellular matrix metalloproteinase inducer in multidrug resistant cancer cells. Molecular Cancer Research, 1(6), 420–427.

    CAS  PubMed  Google Scholar 

  23. Marieb, E. A., et al. (2004). Emmprin promotes anchorage-independent growth in human mammary carcinoma cells by stimulating hyaluronan production. Cancer Research, 64(4), 1229–1232.

    Article  CAS  Google Scholar 

  24. Tsai, W. C., et al. (2007). EMMPRIN and fascin overexpression associated with clinicopathologic parameters of pancreatobiliary adenocarcinoma in Chinese people. APMIS, 115(8), 929–938.

    Article  Google Scholar 

  25. Tsai, W. C., et al. (2006). Increasing EMMPRIN and matriptase expression in hepatocellular carcinoma: tissue microarray analysis of immunohistochemical scores with clinicopathological parameters. Histopathology, 49(4), 388–395.

    Article  Google Scholar 

  26. Brummelkamp, T. R., Bernards, R., & Agami, R. (2002). A system for stable expression of short interfering RNAs in mammalian cells. Science, 296(5567), 550–553.

    Article  CAS  Google Scholar 

  27. Li, M., et al. (2006). Cyclophilin A is overexpressed in human pancreatic cancer cells and stimulates cell proliferation through CD147. Cancer, 106(10), 2284–2294.

    Article  CAS  Google Scholar 

  28. Hou, Q., et al. (2011). Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147. Cancer Science, 102(7), 1287–1292.

    Article  CAS  Google Scholar 

  29. Xu, D., & Hemler, M. E. (2005). Metabolic activation-related CD147-CD98 complex. Molecular and Cellular Proteomics, 4(8), 1061–1071.

    Article  CAS  Google Scholar 

  30. Su, J., Chen, X., & Kanekura, T. (2009). A CD147-targeting siRNA inhibits the proliferation, invasiveness, and VEGF production of human malignant melanoma cells by down-regulating glycolysis. Cancer Letters, 273(1), 140–147.

    Article  CAS  Google Scholar 

  31. Zucker, S., et al. (2001). Tumorigenic potential of extracellular matrix metalloproteinase inducer. American Journal of Pathology, 158(6), 1921–1928.

    Article  CAS  Google Scholar 

  32. Zou, W., et al. (2007). Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to paclitaxel in HO-8910 pm cells. Cancer Letters, 248(2), 211–218.

    Article  CAS  Google Scholar 

  33. Zhao, Y., et al. (2013). The role of EMMPRIN expression in ovarian epithelial carcinomas. Cell Cycle, 12(17), 2899–2913.

    Article  CAS  Google Scholar 

  34. Wang, J., et al. (2012). Knockdown of cyclin D1 inhibits proliferation, induces apoptosis, and attenuates the invasive capacity of human glioblastoma cells. Journal of Neuro-oncology, 106(3), 473–484.

    Article  CAS  Google Scholar 

  35. Grana, X., & Reddy, E. P. (1995). Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene, 11(2), 211–219.

    CAS  PubMed  Google Scholar 

  36. Yang, J. M., et al. (2006). Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim. Journal of Biological Chemistry, 281(14), 9719–9727.

    Article  CAS  Google Scholar 

  37. Kuang, Y. H., et al. (2009). RNA interference targeting the CD147 induces apoptosis of multi-drug resistant cancer cells related to XIAP depletion. Cancer Letters, 276(2), 189–195.

    Article  CAS  Google Scholar 

  38. Zhu, C., et al. (2011). Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to cisplatin in laryngeal carcinoma Hep2 cells. Oncology Reports, 25(2), 425–432.

    CAS  PubMed  Google Scholar 

  39. Li, Q. Q., et al. (2007). Involvement of CD147 in regulation of multidrug resistance to P-gp substrate drugs and in vitro invasion in breast cancer cells. Cancer Science, 98(7), 1064–1069.

    Article  CAS  Google Scholar 

  40. Li, Q. Q., et al. (2007). Up-regulation of CD147 and matrix metalloproteinase-2, -9 induced by P-glycoprotein substrates in multidrug resistant breast cancer cells. Cancer Science, 98(11), 1767–1774.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by National Natural Science Foundation (No. 31470570) and funds from Qingdao University (No. 600201304).

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Medical College, Qingdao University, Qingdao, 266021, Shandong, China

    Hui Gao, Qixiao Jiang, Yantao Han & Chunbo Wang

  2. College of Life Sciences, Chongqing Normal University, Chongqing, 401331, China

    Jianjun Peng

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  1. Hui Gao
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  2. Qixiao Jiang
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  3. Yantao Han
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  4. Jianjun Peng
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  5. Chunbo Wang
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Corresponding authors

Correspondence to Jianjun Peng or Chunbo Wang.

Additional information

Hui Gao and Qixiao Jiang contributed equally to this work.

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Gao, H., Jiang, Q., Han, Y. et al. RETRACTED ARTICLE: shRNA-Mediated EMMPRIN Silencing Inhibits Human Leukemic Monocyte Lymphoma U937 Cell Proliferation and Increases Chemosensitivity to Adriamycin. Cell Biochem Biophys 71, 827–835 (2015). https://doi.org/10.1007/s12013-014-0270-4

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  • DOI: https://doi.org/10.1007/s12013-014-0270-4

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