Abstract
New achievements in the field of cancer treatment are results of recent advances in molecular medicine and gene therapy. Usage of microRNAs (miRNAs) which are small noncoding RNAs is one of the molecular research lines for the diagnosis and treatment of cancers. miRNAs have an important role in post-transcriptional regulation of the gene expression and are involved in cellular activities such as growth, differentiation, cell death and cancer development. One of the miRNAs that showed downregulation in human acute erythroleukemia is hsa-let-7c-5p. Down-regulation of hsa-let-7c-5p has been reported in in vitro studies of different cancers. In the present study, upregulation of hsa-let-7c-5p is performed in human acute erythroleukemia cell line (KG-1) using miRNA mimic. qRT-PCR, MTT assay, Annexin-V, and propidium iodide staining at different time points after miRNA mimic transfection were accomplished to assess the expression level of hsa-let-7c-5p, cell viability, apoptosis and late apoptosis. In addition, the expression level of PBX2 oncogene, a validated target gene of hsa-let-7c-5p, is evaluated by RT-qPCR to show the effectivity of this approach on erythroleukemia cancer cells. Our results can be used in translational medicine for future investigation in acute erythroleukemia and to approach treatment based on miRNA mimic therapy.
Similar content being viewed by others
References
Acevedo-Olvera LF, Diaz-Garcia H, Parra-Barrera A, Caceres-Perez AA, Gutierrez-Iglesias G, Rangel-Corona R, Caceres-Cortes JR (2015) Inhibition of the Na +/H + antiporter induces cell death in TF-1 erythroleukemia cells stimulated by the stem cell factor. Cytokine 75:142–150
Amini-Farsani Z, Sangtarash MH, Shamsara M, Teimori H (2018) MiR-221/222 promote chemoresistance to cisplatin in ovarian cancer cells by targeting PTEN/PI3K/AKT signaling pathway. Cytotechnology 70:203–213
Bader AG, Brown D, Winkler M (2010) The promise of microRNA replacement therapy. Cancer Res 70:7027–7030
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Byrd JC et al (2004) Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv (16)(p13q22) or t (16; 16)(p13; q22): results from CALGB 8461. J Clin Oncol 22:1087–1094
Döhner H, Estey EH, Amadori S et al (2010) Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 115:453–474
Döhner H, Weisdorf DJ, Bloomfield CD (2015) Acute myeloid leukemia. N Engl J Med 373:1136–1152
Döhner H et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129:424–447
Dong C, Ji M, Ji C (2009) Micro-RNAs and their potential target genes in leukemia pathogenesis. Cancer Biol Ther 8:200–205
Dores GM, Devesa SS, Curtis RE, Linet MS, Morton LM (2011) Acute leukemia incidence and patient survival among children and adults in the United States, 2001–2007. Blood 119:34–43
Drakaki A, Iliopoulos D (2009) MicroRNA gene networks in oncogenesis. Curr Genom 10:35–41
Faller M, Guo F (2008) MicroRNA biogenesis: there’s more than one way to skin a cat. Biochim Biophys Acta BBA Gene Regul Mech 1779:663–667
Gambari R, Brognara E, Spandidos DA, Fabbri E (2016) Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: Νew trends in the development of miRNA therapeutic strategies in oncology. Int J Oncol 49:5–32
Gammell P (2007) MicroRNAs: recently discovered key regulators of proliferation and apoptosis in animal cells. Cytotechnology 53:55–63
George G, Mittal RD (2010) MicroRNAs: potential biomarkers in cancer. Indian J Clin Biochem 25:4–14
Gong C et al (2011) Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J Biol Chem 286:19127–19137
Han H, Gu J, Zuo H et al (2012) Let-7c functions as a metastasis suppressor by targeting MMP11 and PBX3 in colorectal cancer. J Pathol 226:544–555
Hasserjian R, Howard J, Wood A, Henry K, Bain B (2001) Acute erythremic myelosis (true erythroleukaemia): a variant of AML FAB-M6. J Clin Pathol 54:205–209
Hertel J, Bartschat S, Wintsche A, Otto C, of the Bioinformatics Computer Lab TS, Stadler PF (2012) Evolution of the let-7 microRNA family. RNA Biol 9:231–241
Johnson SM et al (2005) RAS is regulated by the let-7 microRNA family. Cell 120:635–647
Johnson CD et al (2007) The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res 67:7713–7722
Kavianpour M, Ahmadzadeh A, Shahrabi S, Saki N (2016) Significance of oncogenes and tumor suppressor genes in AML prognosis. Tumor Biol 37:10041–10052
Kloosterman WP, Plasterk RH (2006) The diverse functions of microRNAs in animal development and disease. Dev Cell 11:441–450
Kowal-Vern A, Mazzella FM, Cotelingam JD, Shrit MA, Rector JT, Schumacher HR (2000) Diagnosis and characterization of acute erythroleukemia subsets by determining the percentages of myeloblasts and proerythroblasts in 69 cases. Am J Hematol 65:5–13
Liu L et al (2017) MicroRNA-29c functions as a tumor suppressor by targeting VEGFA in lung adenocarcinoma. Mol Cancer 16:50
Marcucci G, Mrózek K, Bloomfield CD (2005) Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics. Curr Opin Hematol 12:68–75
Mazzella FM, Alvares C, Kowal-Vern A, Schumacher HR (2000) The acute erythroleukemias. Clin Lab Med 20:119–137
Mohammadiasl J, Khosravi A, Shahjahani M, Azizidoost S, Saki N (2016) Molecular and cellular aspects of extramedullary manifestations of acute myeloid leukemia. J Cancer Metastasis Treat 2:44–50
Monica K, Galili N, Nourse J, Saltman D, Cleary ML (1991) PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1. Mol Cell Biol 11:6149–6157
Moskow JJ, Bullrich F, Huebner K, Daar IO, Buchberg AM (1995) Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice. Mol Cell Biol 15:5434–5443
Nadiminty N et al (2012) MicroRNA let-7c is downregulated in prostate cancer and suppresses prostate cancer growth. PLoS ONE 7:e32832
Park S-M et al (2007) Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2. Cell Cycle 6:2585–2590
Pelosi A et al (2013) miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia. Oncogene 32:3648–3654
Reddy SDN, Gajula RP, Pakala SB, Kumar R (2010) MicroRNAs and cancer therapy: the next wave or here to stay? Cancer Biol Ther 9:479–482
Rothschild SI (2014) microRNA therapies in cancer. Mol Cell Ther 2:7
Rowley JD (2008) Chromosomal translocations: revisited yet again. Blood 112:2183–2189
Ruan K, Fang X, Ouyang G (2009) MicroRNAs: novel regulators in the hallmarks of human cancer. Cancer Lett 285:116–126
Santos F et al (2009) Adult acute erythroleukemia: an analysis of 91 patients treated at a single institution. Leukemia 23:2275–2280
Sarver AL, Li L, Subramanian S (2010) MicroRNA miR-183 functions as an oncogene by targeting the transcription factor EGR1 and promoting tumor cell migration. Cancer Res 70:9570–9580
Sharifi M, Salehi R, Gheisari Y, Kazemi M (2014) Inhibition of microRNA miR-92a induces apoptosis and inhibits cell proliferation in human acute promyelocytic leukemia through modulation of p63 expression. Mol Biol Rep 41:2799–2808
Shen W-F, Rozenfeld S, Kwong A, Kömüves LG, Lawrence HJ, Largman C (1999) HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells. Mol Cell Biol 19:3051–3061
Shi Y, Liu C, Liu X, Tang DG, Wang J (2014) The microRNA miR-34a inhibits non-small cell lung cancer (NSCLC) growth and the CD44hi stem-like NSCLC cells. PLoS ONE 9:e90022
Stoicea N, Du A, Lakis DC, Tipton C, Arias-Morales CE, Bergese SD (2016) The MiRNA journey from theory to practice as a CNS biomarker. Front Genet 7:11
Tenen DG (2003) Disruption of differentiation in human cancer: AML shows the way. Nat Rev Cancer 3:89–101
Yuan Y, Kasar S, Underbayev C, Prakash S, Raveche E (2012) MicroRNAs in acute myeloid leukemia and other blood disorders. Leuk Res Treat 2012:603830. https://doi.org/10.1155/2012/603830
Zhao B et al (2014) MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3. Cancer Lett 342:43–51
Zhu X, Wu L, Yao J, Jiang H, Wang Q, Yang Z, Wu F (2015) MicroRNA let-7c inhibits cell proliferation and induces cell cycle arrest by targeting CDC25A in human hepatocellular carcinoma. PLoS ONE 10:e0124266
Acknowledgments
This study was conducted with the financial support of Isfahan University of Medical Sciences (IRAN) with Grant Number 395207.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This study was approved by the local ethics committee of Isfahan University of Medical Sciences (IRAN) and the studies have been approved by the appropriate institutional and/or national research ethics committee and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.
Rights and permissions
About this article
Cite this article
Mortazavi, D., Sharifi, M. Antiproliferative effect of upregulation of hsa-let-7c-5p in human acute erythroleukemia cells. Cytotechnology 70, 1509–1518 (2018). https://doi.org/10.1007/s10616-018-0241-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-018-0241-5