Skip to main content

Advertisement

Log in

Aberrant Expression of Some Circulating miRNAs in Childhood Acute Lymphoblastic Leukemia

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Acute lymphoblastic leukemia (ALL) is a heterogeneous cancer commonly affecting children due to dysregulation of miRNA expression. In the current study, authors investigated the expression profile for miRNA-125b-1 and miRNA-203 among childhood ALL. Blood samples were collected from newly diagnosed childhood ALL and healthy control children. The expression profile for candidate miRNAs was detected using quantitative RT-PCR analysis. Statistical analysis were performed using receiver operating characteristic curve (ROC) to examine the diagnostic efficacy of the two miRNA and their levels among ALL clinicopathological factors and phenotypes. The median expression level for miRNA-125b-1 was significantly high in childhood ALL; while miRNA-203 level was significantly low in childhood ALL as compared to control ones. MiRNA-125-1 reported significant increase in T-ALL as compared to other ALL phenotypes. Median miRNA-203 level was high in T-ALL followed by pre-B-ALL although no significant difference was reported. Clinicopathological factors did not emphasize significance with either detected miRNAs. Using ROC curve the diagnostic efficacy was significant with an area under the curve 0.858 for miRNA-125b-1 (83.72, 100%) and 0.878 for miRNA-203 (97.67, 86.96%). The combination of the two key miRNAs revealed absolute sensitivity (100%). MiRNA-125b-1 and miRNA-203 can be useful molecular markers for diagnosis of ALL. Further studies with large cohort are warranted to validate these results.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • American Cancer Society (2013) Cancer facts and figures 2013. American Cancer Society, Atlanta

    Google Scholar 

  • Banzhaf-Strathmann J, Edbauer D (2014) Good guy or bad guy: the opposing roles of microRNA-125b in cancer. Cell Commun Signal 12:30–43

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Boldrup L, Coates PJ, Wahlgren M, Laurell G, Nylander K (2012) Subsite-based alterations in miR-21, miR-125b, and miR-203 in squamous cell carcinoma of the oral cavity and correlation to important target proteins. J Carcinog 11:18

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bousqueta M, Harrisb MH, Zhoua B, Lodisha HF (2010) MicroRNA miR-125b causes leukemia. PNAS 107:21558–21563

    Article  Google Scholar 

  • Bueno MJ, de Castrode IP, de Cedron MG, Santos J, Calin GA, Cigudosa JC, Croce CM, Piqueras JF, Malumbres M (2003) Genetic and epigenetic silencing of MicroRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression. Cancer Cell 13:496–506

    Article  CAS  Google Scholar 

  • Carroll WL, Raetz EA (2012) Clinical and laboratory biology of childhood acute lymphoblastic leukemia. J Pediateric 160:10–18

    Article  Google Scholar 

  • Duyu M, Durmaz B, Gunduz C, Yergin C, Karapinar Y, Aksoylar S, kavaki K, Cetingul N, Yaman Y, Ozkiany F, Cogulu O (2014) Prospective evaluation of whole genome MicroRNA expression profiling in childhood acute lymphoblastic leukemia. Biomed Res Int. https://doi.org/10.1155/2014/967585

    Article  PubMed  PubMed Central  Google Scholar 

  • Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with arole in cancer. Nat Rev Cancer 6:259–269

    Article  PubMed  CAS  Google Scholar 

  • Fatica A, Fazi F (2013) MicroRNA-regulated pathways in hematological malignancies: how to avoid cells playing out of tune. Int J Mol Sci 14:20930–20953

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Garzon R, Marcucci G, Croce CM (2010) Targeting microRNAsin cancer: rationale, strategies and challenges. Nat Rev Drug Discov 9(10):775–789

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grasedieck S, Sorrentino A, Langer C, Buske C, Döhner H, Mertens D, Kuchenbaue F (2013) Circulating microRNAs in hematological diseases: principles, challenges, and perspectives. Blood 121(25):4977–4984

    Article  PubMed  CAS  Google Scholar 

  • Hobert O (2008) Gene regulation by transcription factors and microRNAs. Science 319:1785–1786

    Article  PubMed  CAS  Google Scholar 

  • Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H (2014) Cancer incidence in Egypt: results of the National Population-Based Cancer Registry Program. J Cancer Epidemiol. https://doi.org/10.1155/2014/437971

    Article  PubMed  PubMed Central  Google Scholar 

  • Imaoka H, Toiyama Y, Okigami M, Yasuda H, Saigusa S, Ohi M, Tanaka K, Inoue Y, Mohri Y, Kusunoki M (2016) Circulating microRNA-203 predicts metastases, early recurrence, and poor prognosis in human gastric cancer. Gastric Cancer 19:744–753

    Article  PubMed  CAS  Google Scholar 

  • Jaffe ES, Harris NL, Stein H, Vardiman JW (2001) World Health Organisation classification of tumors, pathology and genetics: tumors of haematopoietic and lymphoid tissues. IARC Press, Lyon

    Google Scholar 

  • Li J, Wan Y, Ji Q, Wu Y (2013) The role of microRNAs in B-cell development and function. Cell Mol Immunol 10:107–112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Li Q, Liu L, Li W (2014a) Identification of circulating microRNAs as biomarkers in diagnosis of hematologic cancers: a meta-analysis. Tumour Biol 35(10):10467–10478

    Article  PubMed  CAS  Google Scholar 

  • Li WY, Chen XM, Xiong W, Guo DM, Lu L, Li HY (2014b) Detection of microvesicle miRNA expression in ALL subtypes and analysis of their functional roles. J Huazhong Univ Sci Technol Med Sci 34(5):640–645

    Article  PubMed  CAS  Google Scholar 

  • Luan C, Yang Z, Chen B (2015) The functional role of microRNA in acute lymphoblastic leukemia: relevance for diagnosis, differential diagnosis, prognosis, and therapy. Oncotargets Ther 8:2903–2914

    CAS  Google Scholar 

  • Pui CH, Robison LL, Look AT (2008) Acute lymphoblastic leukaemia. Lancet 371(3):1030–1043

    Article  PubMed  CAS  Google Scholar 

  • Ramani R, Megason G, Schalheim J, Karlson C, Vijayakumar V, Vijayakumar S, Hicks C (2017) Integrative analysis of miRNA-mediated gene signatures and pathways modulating white blood cell count in childhood acute lymphoblastic leukemia. Biomarkers Insight 17:1–12

    Google Scholar 

  • Randolph TR (2004) Advances in acute lymphoblastic leukemia. Clin Lab Sci 17(4):235–245

    PubMed  Google Scholar 

  • Redshaw N, Wilkes N, Whale A, Cowen S, Huggett J, Foy CA (2013) A comparison of miRNA: isolation and RT-qPCR technologies and their effects on quantification accuracy and repeatability. Bio Tech 54:155–164

    CAS  Google Scholar 

  • Saki N, Abroun S, Hajizamani S, Rahim F, Shahjahani M (2014) Association of chromosomal translocation and MiRNA expression with the pathogenesis of multiple myeloma. Cell J (Yakhteh) 16(2):99–110

    CAS  Google Scholar 

  • Schotte D, Pieters R, Den Boer ML (2012) MicroRNAs in acute leukemia: from biological players to clinical contributors. Leukemia 26:1–12

    Article  PubMed  CAS  Google Scholar 

  • Shaham L, Binder V, Gefen N, Borkhardt A, Izraeli S (2012) MiR-125 in normal and malignant hematopoiesis. Leukemia 26:2011–2018

    Article  PubMed  CAS  Google Scholar 

  • Stumpe DJPM, Schotte D, Lange-Turenhout EAM, Schneider P, Seslija L, de Menezes RX, Pieters R, den Boer ML, Stam RW (2011) Hypermethylation of specific microRNA genes in MLL-rearranged infant acute lymphoblastic leukemia: major matters at a micro scale. Leukemia 25:429–439

    Article  CAS  Google Scholar 

  • Tang R, Zhong T, Dang Y, Zhang X, Li P, Chen G (2016) Association between downexpression of MiR-203 and poor prognosis in non-small cell lung cancer patients. Clin Transl Oncol 18:360–368

    Article  PubMed  CAS  Google Scholar 

  • Wallaert A, Loocke WV, Hernandez L, Taghon T, Speleman F, Vlierberghe PV (2017) Comprehensive miRNA expression profiling in human T-cell acute lymphoblastic leukemia by small RNA-sequencing. Sci Rep 7:7901. https://doi.org/10.1038/s41598-017-08148-x

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wang S, Zhao X, Wang J, Wen Y, Zhang L, Wang D, Chen H, Chen Q, Xiang W (2013) Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer. Med Oncol 30:681–687

    Article  PubMed  CAS  Google Scholar 

  • Wang N, Liang H, Zhou Y, Wang C, Zhang S, Pan Y, Wang Y, Yan X, Zhang J, Zhang C-Y, Zen K, Li D, Chen X (2014) MiR-203 suppresses the proliferation and migration and promotes the apoptosis of lung cancer cells by targeting SRC. PLoS ONE 9(8):e105570

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zhang Y, Yan LX, Wu QN, Du ZM, Chen J, Liao DZ, Huang MY, Hou JH, Wu QL, Zeng MS, Huang WL, Zeng YX, Shao YJ (2011) MiR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 protooncogene in human invasive breast cancer. Cancer Res 71(10):1–11

    Article  Google Scholar 

  • Zhao S, Yao D, Chen J, Ding N (2013) Aberrant expression of miR-20a and miR-203 in cervical cancer. Asian Pac J Cancer Prev 14(4):2289–2293

    Article  PubMed  Google Scholar 

  • Zhu T, Gao W, Chen X, Zhang Y, Wu M, Zhang P, Wang S (2016) A pilot study of circulating MicroRNA-125b as a diagnostic and prognostic biomarker for epithelial ovarian cancer. Int J Gynecol Cancer. https://doi.org/10.1097/IGC.0000000000000846

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgement

This work was partially funded through National Research Centre, Giza, Egypt.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Menha Swellam.

Ethics declarations

Conflict of interest

The authors report no conflict of interest in this work.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Swellam, M., Hashim, M., Mahmoud, M.S. et al. Aberrant Expression of Some Circulating miRNAs in Childhood Acute Lymphoblastic Leukemia. Biochem Genet 56, 283–294 (2018). https://doi.org/10.1007/s10528-018-9844-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-018-9844-y

Keywords

Navigation