MicroRNAs (miRNAs or miRs) are small molecules known to be involved in post-transcriptional gene expression. Many of them have been shown to influence risk for various diseases. Recent studies suggest that lower expression of miR-204, a gene coding for miRNA-204, is correlated with shorter survival in patients with acute myeloid leukaemia (AML). This observation prompted us to analyse the effect of two polymorphisms of the miR-204 gene, one in the upstream flanking region (rs718447 A > G) and the other inside the gene itself (rs112062096 A > G), both also in intron 3 of the TRPM3 gene.
The study was conducted on DNA samples isolated from AML patients (n = 95) and healthy individuals (n = 148), who were genotyped using the Light SNiP assays.
The miR-204 rs718447 GG homozygosity was found to constitute a risk factor associated with susceptibility to AML (73/95 vs 92/148, AML patients vs healthy controls, OR = 2.020, p = 0.017). Additionally, this genotype was more frequent in patients with subtypes M0-M1 in the French-American-British (FAB) classification as compared to patients with subtypes M2-M7 (23/25 vs 39/57, p = 0.026). We also found that presence of allele A was linked to longer survival of AML patients.
Our results show that polymorphism in miR-204 flanking region may constitute a risk and prognostic factor in AML.
Khaled S, Al Malki M, Marcucci G. Acute Myeloid Leukemia: Biologic, Prognostic, and Therapeutic Insights. Oncology. 2016;30(4):318–29. PubMed
Liu H, Zhou Y, Liu Q, Xiao G, Wang B, Li W, Ye D, Yu S. Association of miR-608 rs4919510 polymorphism and cancer risk: a meta-analysis based on 13,664 subjects. Oncotarget. 2016;8(23):37023–31. PubMedCentral
Chung TK, Lau TS, Cheung TH, Yim SF, Lo KW, Siu NS, Chan LK, Yu MY, Kwong J, Doran G, Barroilhet LM, Ng AS, Wong RR, Wang VW, Mok SC, Smith DI, Berkowitz RS, Wong YF. Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1. Int J Cancer. 2012;130(5):1036–45. CrossRefPubMed
Sacconi A, Biagioni F, Canu V, Mori F, Di Benedetto A, Lorenzon L, Ercolani C, Di Agostino S, Cambria AM, Germoni S, Grasso G, Blandino R, Panebianco V, Ziparo V, Federici O, Muti P, Strano S, Carboni F, Mottolese M, Diodoro M, Pescarmona E, Garofalo A, Blandino G. miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer. Cell Death Dis. 2012;3:e423. CrossRefPubMedPubMedCentral
Duan S, Wu A, Chen Z, Yang Y, Liu L, Shu Q. MiR-204 regulates cell proliferation and invasion by targeting EphB2 in human cervical cancer. Oncol Res. 2017; doi: 10.3727/096504017X15016337254641.
Yuan X, Wang S, Liu M, Lu Z, Zhan Y, Wang W, Xu AM. Histological and pathological assessment of miR-204 and SOX4 levels in gastric cancer patients. Biomed Res Int 2017;2017: 6894675.
- Genetic variation of the gene coding for microRNA-204 (miR-204) is a risk factor in acute myeloid leukaemia
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II