BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

MiR-204 acts as a potential therapeutic target in acute myeloid leukemia by increasing BIRC6-mediated apoptosis

  • Wang, Zhiguo (Department of Hematology, the First Affiliated Hospital of Xi'an Jiaotong University) ;
  • Luo, Hong (Department of Hematology, the First Hospital of Qiqihar) ;
  • Fang, Zehui (Department of Endocrinology, the 4th Affiliated Hospital of Harbin Medical University) ;
  • Fan, Yanling (Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital) ;
  • Liu, Xiaojuan (Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital) ;
  • Zhang, Yujing (Department of Endocrinology, the 4th Affiliated Hospital of Harbin Medical University) ;
  • Rui, Shuping (Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital) ;
  • Chen, Yafeng (Department of Bone Marrow Transplantation, Harbin Hematological Cancer Institute, Harbin the First Hospital) ;
  • Hong, Luojia (Department of Endocrinology, the 4th Affiliated Hospital of Harbin Medical University) ;
  • Gao, Jincheng (Department of Endocrinology, the 4th Affiliated Hospital of Harbin Medical University) ;
  • Zhang, Mei (Department of Hematology, the First Affiliated Hospital of Xi'an Jiaotong University)
  • Received : 2018.02.15
  • Accepted : 2018.04.23
  • Published : 2018.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Acute myeloid leukemia (AML) is one of the most common hematological malignancies all around the world. MicroRNAs have been determined to contribute various cancers initiation and progression, including AML. Although microRNA-204 (miR-204) exerts anti-tumor effects in several kinds of cancers, its function in AML remains unknown. In the present study, we assessed miR-204 expression in AML blood samples and cell lines. We also investigated the effects of miR-204 on cellular function of AML cells and the underlying mechanisms of the action of miR-204. Our results showed that miR-204 expression was significantly downregulated in AML tissues and cell lines. In addition, overexpression of miR-204 induced growth inhibition and apoptosis in AML cells, including AML5, HL-60, Kasumi-1 and U937 cells. Cell cycle analysis further confirmed an augmentation in theapoptotic subG1 population by miR-204 overexpression. Mechanistically, baculoviral inhibition of apoptosis protein repeat containing 6 (BIRC6) was identified as a direct target of miR-204. Enforcing miR-204 expression increased the luciferase activity and expression of BIRC6, as well as p53 and Bax expression. Moreover, restoration of BIRC6 reversed the pro-apoptotic effects of miR-204 overexpression in AML cells. Taken together, this study demonstrates that miR-204 causes AML cell apoptosis by targeting BIRC6, suggesting miR-204 may play an anti-carcinogenic role in AML and function as a novel biomarker and therapeutic target for the treatment of this disease.

Keywords

References

  1. Fulda S (2014) Inhibitor of Apoptosis (IAP) proteins in hematological malignancies: molecular mechanisms and therapeutic opportunities. Leukemia 28, 1414-1422 https://doi.org/10.1038/leu.2014.56
  2. Chen Z, Naito M, Hori S, Mashima T, Yamori T and Tsuruo T (1999) A human IAP-family gene, apollon, expressed in human brain cancer cells. Biochem Biophys Res Commun 264, 847-854 https://doi.org/10.1006/bbrc.1999.1585
  3. Martin SJ (2004) An Apollon vista of death and destruction. Nat Cell Biol 6, 804-806 https://doi.org/10.1038/ncb0904-804
  4. Ismail EA, Mahmoud HM, Tawfik LM et al (2012) BIRC6/Apollon gene expression in childhood acute leukemia: impact on therapeutic response and prognosis. Eur J Haematol 88, 118-127 https://doi.org/10.1111/j.1600-0609.2011.01734.x
  5. Sung KW, Choi J, Hwang YK et al (2007) Overexpression of Apollon, an antiapoptotic protein, is associated with poor prognosis in childhood de novo acute myeloid leukemia. Clin Cancer Res 13, 5109-5114 https://doi.org/10.1158/1078-0432.CCR-07-0693
  6. Lopergolo A, Pennati M, Gandellini P et al (2009) Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation. Br J Cancer 100, 739-746 https://doi.org/10.1038/sj.bjc.6604927
  7. Tang W, Xue R, Weng S et al (2015) BIRC6 promotes hepatocellular carcinogenesis: interaction of BIRC6 with p53 facilitating p53 degradation. Int J Cancer 136, E475-487 https://doi.org/10.1002/ijc.29194
  8. Shrestha S, Yang CD, Hong HC et al (2017) Integrated MicroRNA-mRNA Analysis Reveals miR-204 Inhibits Cell Proliferation in Gastric Cancer by Targeting CKS1B, CXCL1 and GPRC5A. Int J Mol Sci 19
  9. Shu Y, Ren L, Xie B, Liang Z and Chen J (2017) MiR-204 enhances mitochondrial apoptosis in doxorubicin-treated prostate cancer cells by targeting SIRT1/p53 pathway. Oncotarget 8, 97313-97322
  10. Song CJ, Chen H, Chen LZ, Ru GM, Guo JJ and Ding QN (2017) The potential of microRNAs as human prostate cancer biomarkers: A meta-analysis of related studies. J Cell Biochem 119, 2763-2786
  11. Zhu X, Shen H, Yin X et al (2017) IL-6R/STAT3/miR-204 feedback loop contributes to cisplatin resistance of epithelial ovarian cancer cells. Oncotarget 8, 39154-39166
  12. Yin Y, Zhang B, Wang W et al (2014) miR-204-5p inhibits proliferation and invasion and enhances chemotherapeutic sensitivity of colorectal cancer cells by downregulating RAB22A. Clin Cancer Res 20, 6187-6199 https://doi.org/10.1158/1078-0432.CCR-14-1030
  13. Duan S, Wu A, Chen Z, Yang Y, Liu L and Shu Q (2017) MiR-204 Regulates Cell Proliferation and Invasion by Targeting EphB2 in Human Cervical Cancer. Oncol Res 26, 713-723
  14. Diaz-Martinez M, Benito-Jardon L, Alonso L, Koetz-Ploch L, Hernando E and Teixido J (2017) miR-204-5p and miR-211-5p contribute to BRAF inhibitor resistance in melanoma. Cancer Res 78, 1017-1030
  15. Luo YH, Tang W, Zhang X et al (2017) Promising significance of the association of miR-204-5p expression with clinicopathological features of hepatocellular carcinoma. Medicine (Baltimore) 96, e7545 https://doi.org/10.1097/MD.0000000000007545
  16. Reubold TF and Eschenburg S (2012) A molecular view on signal transduction by the apoptosome. Cell Signal 24, 1420-1425 https://doi.org/10.1016/j.cellsig.2012.03.007
  17. Li T, Pan H and Li R (2016) The dual regulatory role of miR-204 in cancer. Tumour Biol 37, 11667-11677 https://doi.org/10.1007/s13277-016-5144-5
  18. Roldo C, Missiaglia E, Hagan JP et al (2006) MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol 24, 4677-4684 https://doi.org/10.1200/JCO.2005.05.5194
  19. Zanette DL, Rivadavia F, Molfetta GA et al (2007) miRNA expression profiles in chronic lymphocytic and acute lymphocytic leukemia. Braz J Med Biol Res 40, 1435-1440 https://doi.org/10.1590/S0100-879X2007001100003
  20. Jin Z and El-Deiry WS (2005) Overview of cell death signaling pathways. Cancer Biol Ther 4, 139-163
  21. Chu L, Gu J, Sun L, Qian Q, Qian C and Liu X (2008) Oncolytic adenovirus-mediated shRNA against Apollon inhibits tumor cell growth and enhances antitumor effect of 5-fluorouracil. Gene Ther 15, 484-494 https://doi.org/10.1038/gt.2008.6
  22. Choi H, Lee H, Kim SR, Gho YS and Lee SK (2013) Epstein-Barr virus-encoded microRNA BART15-3p promotes cell apoptosis partially by targeting BRUCE. J Virol 87, 8135-8144 https://doi.org/10.1128/JVI.03159-12
  23. Crippa E, Folini M, Pennati M, Zaffaroni N, Pierotti MA and Gariboldi M (2016) miR-342 overexpression results in a synthetic lethal phenotype in BRCA1-mutant HCC1937 breast cancer cells. Oncotarget 7, 18594-18604
  24. Druz A, Chu C, Majors B, Santuary R, Betenbaugh M and Shiloach J (2011) A novel microRNA mmu-miR-466h affects apoptosis regulation in mammalian cells. Biotechnol Bioeng 108, 1651-1661 https://doi.org/10.1002/bit.23092
  25. Van Houdt WJ, Emmink BL, Pham TV et al (2011) Comparative proteomics of colon cancer stem cells and differentiated tumor cells identifies BIRC6 as a potential therapeutic target. Mol Cell Proteomics 10, M111 011353 https://doi.org/10.1074/mcp.M111.011353
  26. Bartke T, Pohl C, Pyrowolakis G and Jentsch S (2004) Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell 14, 801-811 https://doi.org/10.1016/j.molcel.2004.05.018
  27. Okumu DO, East MP, Levine M et al (2017) BIRC6 mediates imatinib resistance independently of Mcl-1. PLoS One 12, e0177871 https://doi.org/10.1371/journal.pone.0177871