Abstract
Accumulating data indicate that cancer stem cells play an important role in tumorigenesis and are underlying cause of tumor recurrence and metastasis, specifically in chronic myeloid leukemia (CML). We aim to detect the miRNAs that are correlated with the cancer stem cells in CML to provide theoretical basis for clinical application. We first analyzed microRNA expression profiles of CML leukemia patients compared with normal controls by microarray analysis and validated the results by real-time PCR. A single microRNA signature classified CML from normal was detected. We also determined the absolute copy numbers of these three microRNAs in normal adults. The results showed that three microRNAs (miR-150, miR-23a, and miR-130a) were identified to significantly decrease in expanded 38 CML patients compared with 90 normal controls. Molecular and statistical analysis showed that the decreased microRNAs were significant in clinical analysis. All these results indicated that those three microRNAs could act as a tumor suppressor and their decreased expression might be one of the causes of leukemia. Accordingly, clarifying their regulatory mechanisms might delineate their potentials as drug targets of gene therapy for CML.
Similar content being viewed by others
Abbreviations
- CML:
-
Chronic myeloid leukemia
- Ph:
-
Philadelphia
- AP:
-
Ammonium persulfate
- PHA:
-
Polyhydroxyalkanoates
- MNC:
-
Mononuclear cell
References
Barnes DJ, Melo JV (2006) Primitive, quiescent and difficult to kill: the role of non-proliferating stem cells in chronic myeloid leukemia. Cell Cycle 5:2862–2866
Jørgensen HG, Allan EK, Jordanides NE, Mountford JC, Holyoake TL (2007) Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells. Blood 109:4016–4019
Jørgensen HG, Copland M, Allan EK, Jiang X, Eaves A, Eaves C (2006) Intermittent exposure of primitive quiescent chronic myeloid leukemia cells to granulocyte-colony stimulating factor in vitro promotes their elimination by imatinib mesylate. Clin Cancer Res 12:626–633
Xishan Z, Xinna Z, Baoxin H, Jun R (2013) Impaired immunomodulatory function of chronic myeloid leukemia cancer stem cells and the possible mechanism involved in it. Cancer Immunol Immunother 62(4):689–703
Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-β and promotes tumor invasion and angiogenesis. Genes Dev 14:163–176
Fridman R, Toth M, Chvyrkova I, Meroueh S, Mobashery S (2003) Cell surface association of matrix metalloproteinase-9 (gelatinase B). Cancer Metastasis Rev 22:153–166
Xishan Z, Xu Z, Lawei Y, Gang L (2012) Hemangioblastic characteristics of cancer stem cells in chronic myeloid leukemia. Clin Lab 58(7–8):607–613
Paupert J, Mansat-De Mas V, Demur C (2008) Cell-surface MMP-9 regulates the invasive capacity of leukemia blast cells with monocytic features. Cell Cycle 7(8):1047–1053
Fatica A, Fazi F (2013) MicroRNA-regulated pathways in hematological malignancies: how to avoid cells playing out of tune. Int J Mol Sci 14(10):20930–20953
Redondo-Muñoz J, Escobar-Díaz E, Samaniego R (2006) MMP-9 in B-cell chronic lymphocytic leukemia is up-regulated by alpha4beta1 integrin or CXCR4 engagement via distinct signaling pathways, localizes to podosomes, and is involved in cell invasion and migration. Blood 108(9):3143–3151
Shishodia S, Sethi G, Konopleva M, Andreeff M, Aggarwal BB (2006) A synthetic triterpenoid, CDDO-Me, inhibits IkappaBalpha kinase and enhances apoptosis induced by TNF and chemotherapeutic agents through down-regulation of expression of nuclear factor kappaB-regulated gene products in human leukemic cells. Clin Cancer Res 12(6):1828–1838
Janowska-Wieczorek A, Majka M, Marquez-Curtis L, Wertheim JA, Turner AR, Ratajczak MZ (2002) BCR–ABL-positive cells secrete angiogenic factors including matrix metalloproteinases and stimulate angiogenesis in vivo in Matrigel implants. Leukemia 16(6):1160–1166
Kaneta Y, Kagami Y, Tsunoda T, Ohno R, Nakamura Y, Katagiri T (2003) Genome-wide analysis of gene-expression profiles in chronic myeloid leukemia cells using a cDNA microarray. Int J Oncol 23(3):681–691
Bruchova H, Borovanova T, Klamova H, Brdicka R (2002) Gene expression profiling in chronic myeloid leukemia patients treated with hydroxyurea. Leuk Lymphoma 43(6):1289–1295
Ries C, Loher F, Zang C, Ismair MG, Petrides PE (1999) Matrix metalloproteinase production by bone marrow mononuclear cells from normal individuals and patients with acute and chronic myeloid leukemia or myelodysplastic syndromes. Clin Cancer Res 5(5):1115–1124
Guo P, Nie Q, Lan J, Ge J, Qiu Y, Mao Q (2013) C-Myc negatively controls the tumor suppressor PTEN by upregulating miR-26a in glioblastoma multiforme cells. Biochem Biophys Res Commun 441(1):186–190
Miska EA, Alvarez-Saavedra E, Townsend M et al (2004) Microarray analysis of microRNA expression in the developing mammalian brain. Genome Biol 5(9):R68
Sun Y, Koo S, White N et al (2004) Development of a micro-array to detect human and mouse microRNAs and characterization of expression in human organs. Nucleic Acids Res 32:e188
Teichler S, Illmer T, Roemhild J, Ovcharenko D, Stiewe T, Neubauer A (2011) MicroRNA29a regulates the expression of the nuclear oncogene Ski. Blood 118(7):1899–1902
Krichevsky AM, King KS, Donahue CP et al (2003) A microRNA array reveals extensive regulation of microRNAs during brain development. RNA 9(10):1274–1281
Liang RQ, Li W, Li Y et al (2005) An oligonucleotide microarray for microRNA expression analysis based on labeling RNA with quantum dot and nanogold probe. Nucleic Acids Res 33:e17
Thomson JM, Parker J, Perou CM et al (2004) A custom microarray platform for analysis of microRNA gene expression. Nat Methods 1:47–53
Nelson PT, Baldwin DA, Scearce LM et al (2004) Microarray-based, high-throughput gene expression profiling of microRNAs. Nat Methods 1(2):155–161
Baskerville S, Bartel DP (2005) Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA 11:241–247
Pouladi N, Kouhsari SM, Feizi MH, Gavgani RR, Azarfam P (2013) Overlapping region of p53/Wrap53 transcripts: mutational analysis and sequence similarity with microRNA-4732-5p. Asian Pac J Cancer Prev 14(6):3503–3507
Wang L, Li B, Li L, Wang T (2013) MicroRNA-497 suppresses proliferation and induces apoptosis in prostate cancer cells. Asian Pac J Cancer Prev 14(6):3499–3502
Xing HJ, Li YJ, Ma QM, Wang AM, Wang JL, Sun M, Jian Q, Hu JH, Li D, Wang L (2013) Identification of microRNAs present in congenital heart disease associated copy number variants. Eur Rev Med Pharmacol Sci 17(15):2114–2120
Li X, Zhang X, Wang T, Sun C, Jin T, Yan H, Zhang J, Li X, Geng T, Chen C, Ma A, Li S (2013) Regulation by bisoprolol for cardiac microRNA expression in a rat volume-overload heart failure model. J Nanosci Nanotechnol 13(8):5267–5275
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(39):13944–13949
Cheng AM, Byrom MW, Shelton J et al (2005) Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33(4):1290–1297
Mansfield JH, Harfe BD, Nissen R et al (2004) MicroRNA-responsive ‘sensor’ transgenes uncover Hox-like and other developmentally regulated patterns of vertebrate microRNA expression. Nat Genet 36(10):1079–1083
Felli N, Fontana L, Pelosi E et al (2005) MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation. Proc Natl Acad Sci USA 102(50):18081–18086
Karaayvaz M, Zhai H, Ju J (2013) miR-129 promotes apoptosis and enhances chemosensitivity to 5-fluorouracil in colorectal cancer. Cell Death Dis 4:e659. doi:10.1038/cddis.2013.193
Zhang J, Zhang D, Wu GQ, Feng ZY, Zhu SM (2013) Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression. Hepatobiliary Pancreat Dis Int 12(3):305–309
Ma D, Tao X, Gao F, Fan C, Wu D (2012) miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling. Oncol Lett 4(3):483–488
Goedeke L, Vales-Lara FM, Fenstermaker M, Cirera-Salinas D, Chamorro-Jorganes A, Ramírez CM, Mattison JA, de Cabo R, Suárez Y, Fernández-Hernando C (2013) A regulatory role for microRNA 33* in controlling lipid metabolism gene expression. Mol Cell Biol 33(11):2339–2352. doi:10.1128/MCB.01714-12
Cheng C, Li W, Zhang Z, Yoshimura S, Hao Q, Zhang C, Wang Z (2013) MicroRNA-144 is regulated by activator protein-1 (AP-1) and decreases expression of Alzheimer disease-related a disintegrin and metalloprotease 10 (ADAM10). J Biol Chem 288(19):13748–13761. doi:10.1074/jbc.M112.381392
Kiriakidou M, Nelson PT, Kouranov A et al (2004) A combined computational experimental approach predicts human microRNA targets. Genes Dev 18:1165–1178
Krek A (2005) Combinatorial microRNA target predictions. Nat Genet 37:495–500
Grun D, Wang Y, Langenberger D et al (2005) microRNA Target predictions across seven Drosophila species and comparison to mammalian targets. PLoS Comput Biol 1:e13
Acknowledgments
The research is funded by the National Science Foundation (81100366) and Beijing Nova Programme (2013041).
Conflict of interest
There is no conflict of interest to declare.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Zhu, X., Lin, Z., Du, J. et al. Studies on microRNAs that are correlated with the cancer stem cells in chronic myeloid leukemia. Mol Cell Biochem 390, 75–84 (2014). https://doi.org/10.1007/s11010-013-1958-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11010-013-1958-2