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Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute myeloid leukemia

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Abstract

A genome-wide serum miRNA expression analysis previously showed the upregulation of microRNA-375 (miR-375) in acute myeloid leukemia (AML) patients compared with healthy controls. The aim of this study was to investigate the expression patterns and the prognostic relevance of miR-375 in pediatric AML. Expression levels of miR-375 in bone marrow mononuclear cells were detected by real-time quantitative PCR in a cohort of 106 patients with newly diagnosed pediatric AML. Expression levels of miR-375 in the bone marrow of pediatric AML patients were significantly higher than those in normal controls (P < 0.001). Then, miR-375 upregulation occurred more frequently in French–American–British classification subtype M7 than in other subtypes (P < 0.001). Regarding to cytogenetic risk, the expression levels of miR-375 in pediatric AML patients with unfavorable karyotypes were dramatically higher than those in intermediate and favorable groups (P = 0.002). Moreover, high miR-375 expression was significantly associated with shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001) in pediatric AML patients. Multivariate analysis further identified miR-375 expression and cytogenetics risk as independent prognostic factors for both relapse-free survival and overall survival. In particular, the prognostic relevance of miR-375 expression was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Our findings suggest for the first time that the upregulation of miR-375 may be one of the molecular mechanisms involved in the development and progression of pediatric AML. Since its correlation with poor relapse-free survival and overall survival, miR-375 may be a novel biomarker to improve the management of pediatric AML patients.

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References

  1. Estey EH (2013) Acute myeloid leukemia: 2013 update on risk-stratification and management. Am J Hematol 88:318–327

    Article  PubMed  CAS  Google Scholar 

  2. Ganetsky A (2012) The role of decitabine for the treatment of acute myeloid leukemia. Ann Pharmacother 46:1511–1517

    Article  PubMed  Google Scholar 

  3. Puumala SE, Ross JA, Aplenc R, Spector LG (2013) Epidemiology of childhood acute myeloid leukemia. Pediatr Blood Cancer 60:728–733

    Article  PubMed  Google Scholar 

  4. Danen-van Oorschot AA, Kuipers JE, Arentsen-Peters S et al (2012) Differentially expressed miRNAs in cytogenetic and molecular subtypes of pediatric acute myeloid leukemia. Pediatr Blood Cancer 58:715–721

    Article  PubMed  Google Scholar 

  5. Liu X, Liu L, Xu Q, Wu P, Zuo X, Ji A (2012) MicroRNA as a novel drug target for cancer therapy. Expert Opin Biol Ther 12:573–580

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  7. van Kouwenhove M, Kedde M, Agami R (2011) MicroRNA regulation by RNA binding proteins and its implications for cancer. Nat Rev Cancer 11:644–656

    Article  PubMed  Google Scholar 

  8. Dela Cruz F, Matushansky I (2011) MicroRNAs in chromosomal translocation associated solid tumors: learning from sarcomas. Discov Med 12:307–317

    PubMed  Google Scholar 

  9. Jansson MD, Lund AH (2012) MicroRNA and cancer. Mol Oncol 6:590–610

    Article  PubMed  CAS  Google Scholar 

  10. Nana-Sinkam SP, Croce CM (2013) Clinical applications for microRNAs in cancer. Clin Pharmacol Ther 93:98–104

    Article  PubMed  CAS  Google Scholar 

  11. Marcucci G, Maharry KS, Metzeler KH et al (2013) Clinical role of microRNAs in cytogenetically normal acute myeloid leukemia: miR-155 upregulation independently identifies high-risk patients. J Clin Oncol 31:2086–2093

    Google Scholar 

  12. Cimmino A, Calin GA, Fabbri M et al (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102:13944–13949

    Article  PubMed  CAS  Google Scholar 

  13. Lopotová T, Záčková M, Klamová H, Moravcová J (2011) MicroRNA-451 in chronic myeloid leukemia: miR-451–BCR–ABL regulatory loop? Leuk Res 35:974–977

    Article  PubMed  Google Scholar 

  14. Bai J, Guo A, Hong Z, Kuai W (2012) Upregulation of microRNA-100 predicts poor prognosis in patients with pediatric acute myeloid leukemia. Onco Targets Ther 5:213–219

    PubMed  Google Scholar 

  15. Zhu C, Wang Y, Kuai W, Sun X, Chen H, Hong Z (2013) Prognostic value of miR-29a expression in pediatric acute myeloid leukemia. Clin Biochem 46:49–53

    Article  PubMed  CAS  Google Scholar 

  16. Zhi F, Cao X, Xie X et al (2013) Identification of circulating microRNAs as potential biomarkers for detecting acute myeloid leukemia. PLoS ONE 8:e56718

    Article  PubMed  CAS  Google Scholar 

  17. Croce CM (2013) MicroRNA dysregulation in acute myeloid leukemia. J Clin Oncol 31:2065–2066

    Google Scholar 

  18. Poy MN, Eliasson L, Krutzfeldt J et al (2004) A pancreatic islet-specific microRNA regulates insulin secretion. Nature 432:226–230

    Article  PubMed  CAS  Google Scholar 

  19. Siow M, Karen-Ng L, Vincent-Chong V et al (2013) Dysregulation of miR-31 and miR-375 expression is associated with clinical outcomes in oral carcinoma. Oral Dis (in press)

  20. Chang C, Shi H, Wang C et al (2012) Correlation of microRNA-375 downregulation with unfavorable clinical outcome of patients with glioma. Neurosci Lett 531:204–208

    Article  PubMed  CAS  Google Scholar 

  21. Xu Y, Deng Y, Yan X, Zhou T (2011) Targeting miR-375 in gastric cancer. Expert Opin Ther Targets 15:961–972

    Article  PubMed  CAS  Google Scholar 

  22. Komatsu S, Ichikawa D, Takeshita H et al (2012) Prognostic impact of circulating miR-21 and miR-375 in plasma of patients with esophageal squamous cell carcinoma. Expert Opin Biol Ther 12(Suppl 1):S53–S59

    Article  PubMed  CAS  Google Scholar 

  23. Wang F, Li Y, Zhou J et al (2011) miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol 179:2580–2588

    Article  PubMed  CAS  Google Scholar 

  24. Yabushita S, Fukamachi K, Tanaka H et al (2012) Circulating microRNAs in serum of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas. Pancreas 41:1013–1018

    Article  PubMed  CAS  Google Scholar 

  25. Li Y, Jiang Q, Xia N, Yang H, Hu C (2012) Decreased expression of microRNA-375 in nonsmall cell lung cancer and its clinical significance. J Int Med Res 40:1662–1669

    Article  PubMed  CAS  Google Scholar 

  26. Chang Y, Yan W, He X et al (2012) miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology 143(177–87):e8

    PubMed  Google Scholar 

  27. Zhao H, Zhu L, Jin Y, Ji H, Yan X, Zhu X (2012) miR-375 is highly expressed and possibly transactivated by achaete–scute complex homolog 1 in small-cell lung cancer cells. Acta Biochim Biophys Sin (Shanghai) 44:177–182

    Article  CAS  Google Scholar 

  28. Dai X, Chiang Y, Wang Z et al (2012) Expression levels of microRNA-375 in colorectal carcinoma. Mol Med Rep 5:1299–1304

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Huai’an Hospital Affiliated of Xuzhou Medical College and Huai’an Second People’s Hospital, 62 Huaihai Road South, Huai’an, 223002, P. R. China

    Zhengyan Wang & Feng Gao

  2. Department of Pediatrics, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, 223300, Jiangsu, P. R. China

    Ze Hong & Weijing Feng

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  1. Zhengyan Wang
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  2. Ze Hong
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  3. Feng Gao
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  4. Weijing Feng
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Correspondence to Weijing Feng.

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Wang, Z., Hong, Z., Gao, F. et al. Upregulation of microRNA-375 is associated with poor prognosis in pediatric acute myeloid leukemia. Mol Cell Biochem 383, 59–65 (2013). https://doi.org/10.1007/s11010-013-1754-z

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  • DOI: https://doi.org/10.1007/s11010-013-1754-z

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