Molecular Biology Reports

, Volume 40, Issue 12, pp 6811–6819 | Cite as

MicroRNA-142-3p inhibits cell proliferation in human acute lymphoblastic leukemia by targeting the MLL-AF4 oncogene

  • Liping Dou
  • Jingxin Li
  • Dehua Zheng
  • Yonghui Li
  • Xiaoning Gao
  • Chengwang Xu
  • Li Gao
  • Lili Wang
  • Li Yu


The mixed-lineage leukemia (MLL)-AF4 fusion protein encoded by the chromosomal translocation t(4;11) predicts a poorer prognosis in acute lymphoblastic leukemia (ALL) than in other MLL-associated leukemias. However, the detailed mechanism underlying regulation of MLL-AF4 expression remains largely unknown. In this study, we showed that microRNA (miR)-142-3p was significantly downregulated in ALL patients expressing MLL-AF4. Upregulation of miR-142-3p decreased MLL-AF4 expression in the RS4;11 leukemic cell line, which suggests that MLL-AF4 is a direct target of miR-142-3p. Ectopic expression of miR-142-3p remarkably suppressed cell proliferation and induced apoptosis in RS4;11 cells expressing the MLL-AF4 fusion protein. We also found that exogenous expression of miR-142-3p strongly reduced the expression of MLL-AF4 target genes such as homeobox A (HOXA)9, HOXA7, and HOXA10 in RS4;11 cells. Taken together, our results indicate that miR-142-3p functions as a growth suppressor in MLL-AF4+ ALL, and its suppressive effects are mediated primarily through repression of MLL-AF4 expression.


miR-142-3p MLL-AF4 Acute lymphoblastic leukemia MicroRNA 



Acute lymphoblastic leukemia




Mixed-lineage leukemia



This work was supported by the Beijing Nova Program (2011114), National Natural Science Foundation of China (Nos. 30800482, 30971297, 81102242,81000221, 81270610 and 90919044), the Beijing Natural Science Foundation of China (No. 7102147 and 7132217), High and New Technology Program of the PLA (2010gxjs091), Capital Medical Development Scientific Research Fund (No. 2007-2040), National Public Health Grand Research Foundation (No. 201202017), the funding of the public health project (Z111107067311070), and the National 973 Project of China (No. 2005CB522400).

Conflict of interest

The authors declare that there is no conflict of interest.

Supplementary material

11033_2013_2798_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 17 kb)


  1. 1.
    Dou L, Zheng D, Li J, Li Y, Gao L, Wang L, Yu L (2012) Methylation mediated repression of microRNA-143 enhances MLL-AF4 oncogene expression. Oncogene 31:507–517PubMedCrossRefGoogle Scholar
  2. 2.
    Thomas M, Gessner A, Vornlocher HP, Hadwiger P, Greil J, Heidenreich O (2005) Targeting MLL-AF4 with short interfering RNAs inhibits clonogenicity and engraftment of t(4;11)-positive human leukemic cells. Blood 106:3559–3566PubMedCrossRefGoogle Scholar
  3. 3.
    Winter J, Jung S, Keller S, Gregory RI, Diederichs S (2009) Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234PubMedCrossRefGoogle Scholar
  4. 4.
    Coskuna E, von der Heidea EK, Schleea C, Kühnla A, Gbugetb N, Hoelzerb D, Hofmannc WK, Thiela E, Baldusa CD (2011) The role of microRNA-196a and microRNA-196b as ERG regulators in acute myeloid leukemia and acute T-lymphoblastic leukemia. Leuk Res 35:208–213CrossRefGoogle Scholar
  5. 5.
    Ding J, Huang S, Wu S, Zhao Y, Liang L, Yan M, Gel C, Yao J, Chen T, Wan D, Wang H, Gu J, Yao M, Li J, Tu H, He X (2010) Gain of miR-151 on chromosome 8q24.3 facilitates tumour cell migration and spreading through downregulating RhoGDIA. Nat Cell Biol 12:390–399PubMedCrossRefGoogle Scholar
  6. 6.
    Li Y, Guessous F, Zhang Y, DiPierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, Lopes B, Schiff D, Purow B, Abounader R (2009) MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res 69:7569–7576PubMedCrossRefGoogle Scholar
  7. 7.
    Lopez-Serra P, Esteller M (2012) DNA methylation-associated silencing of tumor-suppressor microRNAs in cancer. Oncogene 31:1609–1622PubMedCrossRefGoogle Scholar
  8. 8.
    Kotani A, Ha D, Hsieh J, Rao PK, Schotte D, den Boer ML, Armstrong SA, Lodish HF (2009) miR-128b is a potent glucocorticoid sensitizer in MLL-AF4 acute lymphocytic leukemia cells and exerts cooperative effects with miR-221. Blood 114:4169–4178PubMedCrossRefGoogle Scholar
  9. 9.
    Kotani A, Ha D, Schotte D, den Boer ML, Armstrong SA, Lodish HF (2010) A novel mutation in the miR-128b gene reduces miRNA processing and leads to glucocorticoid resistance of MLL-AF4 acute lymphocytic leukemia cells. Cell Cycle 9:1037–1042PubMedCrossRefGoogle Scholar
  10. 10.
    Wang XS, Gong JN, Yu J, Wang F, Zhang XH, Yin XL, Tan ZQ, Luo ZM, Yang GH, Shen C, Zhang JW (2012) MicroRNA-29a and microRNA-142-3p are regulators of myeloid differentiation and acute myeloid leukemia. Blood 119:4992–5004PubMedCrossRefGoogle Scholar
  11. 11.
    Huang B, Zhao J, Lei Z, Shen S, Li D, Shen GX, Zhang GM, Feng ZH (2009) miR-142-3p restricts cAMP production in CD4+CD25 T cells and CD4+CD25+ TREG cells by targeting AC9 mRNA. EMBO Rep 10:180–185PubMedCrossRefGoogle Scholar
  12. 12.
    Lv M, Zhang X, Jia H, Li D, Zhang B, Zhang H, Hong M, Jiang T, Jiang Q, Lu J, Huang X, Huang B (2012) An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-α and cAMP/PKA pathways. Leukemia 26:769–777PubMedCrossRefGoogle Scholar
  13. 13.
    Lin RJ, Xiao DW, Liao LD, Chen T, Xie ZF, Huang WZ, Wang WS, Jiang TF, Wu BL, Li EM, Xu LY (2012) MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma. J Surg Oncol 105:165–182CrossRefGoogle Scholar
  14. 14.
    Sempere LF, Christensen M, Silahtaroglu A, Bak M, Heath CV, Schwartz G, Wells W, Kauppinen S, Cole CN (2007) Altered microRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res 67:11612–11620PubMedCrossRefGoogle Scholar
  15. 15.
    Chen A, Luo M, Yuan G, Yu J, Deng T, Zhang L, Zhou Y, Mitchelson K, Cheng J (2008) Complementary analysis of microRNA and mRNA expression during phorbol 12-myristate 13-acetate (TPA)-induced differentiation of HL-60 cells. Biotechnol Lett 30:2045–2052Google Scholar
  16. 16.
    Merkerova M, Belickova M, Bruchova H (2008) Differential expression of microRNAs in hematopoietic cell lineages. Eur J Haematol 81:304–310PubMedCrossRefGoogle Scholar
  17. 17.
    Ju X, Li X, Shi Q, Hou H, Sun N, Shen B (2009) Differential microRNA expression in childhood B-cell precursor acute lymphoblastic leukemia. Pediatr Hematol Oncol 26:1–10PubMedCrossRefGoogle Scholar
  18. 18.
    Kim D, Song J, Kim S, Kang SS, Jin EJ (2011) MicroRNA-142-3p regulates TGF-b3-mediated region-dependent chondrogenesis by regulating ADAM9. Biochem Biophys Res Commun 414:653–659PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Liping Dou
    • 1
  • Jingxin Li
    • 1
  • Dehua Zheng
    • 2
  • Yonghui Li
    • 1
  • Xiaoning Gao
    • 1
  • Chengwang Xu
    • 1
  • Li Gao
    • 1
  • Lili Wang
    • 1
  • Li Yu
    • 1
  1. 1.Department of HematologyChinese PLA General HospitalBeijingChina
  2. 2.Department of Hepatobiliary Surgery, Organ Transplant CenterChinese PLA 309th HospitalBeijingChina

Personalised recommendations