Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 28;22(1):142.
doi: 10.1186/s12957-024-03415-4.

Association of deletion polymorphism rs10573247 in the HMGA2 gene with the risk of breast cancer: bioinformatic and experimental analyses

Kolsoom Najibi  1 , Mehdi Moghanibashi  2 , Sirous Naeimi  1
Affiliations

Association of deletion polymorphism rs10573247 in the HMGA2 gene with the risk of breast cancer: bioinformatic and experimental analyses

Kolsoom Najibi et al. World J Surg Oncol. .

Abstract

Background: The high mobility group A2 (HMGA2) gene is expressed extensively during early embryonic development but is inactivated in adulthood, and it is also reactivated in various benign and malignant tumors, including breast cancer. We first assessed the potential functional significance of the unstudied deletion polymorphism rs10573247 at the 3'UTR of HMGA2 on miRNA binding using bioinformatic tools, and subsequently, the association between this polymorphism and breast cancer susceptibility was investigated.

Materials and methods: We applied the RNAhybrid tool to predict the functional effects of polymorphism rs10573247 located within the 3' UTR of the HMGA2 gene on miRNA binding. Then, following DNA extraction, 141 breast cancer patients and 123 healthy controls were genotyped for polymorphism rs10573247 using RFLP-PCR with the restriction enzyme Eam1104I.

Results: Our bioinformatic data have shown that polymorphism rs10573247 is located in the region that serves as a potential target site for eight miRNAs binding. Among them, miR-3125 exhibited decreased binding affinity for the allele delTT (MFE = -21.8) when compared to the allele TT (MFE = -23.9), but miR-4476 increased binding affinity for the allele delTT (MFE = -22.4) compared to the allele TT (MFE = -22.2). In addition, our results showed that the genotype TT/delTT (p = 0.005) and the genotype delTT/delTT (p = 0.029) were significantly associated with an increased risk of developing breast cancer compared to the genotype TT/TT using RFLP-PCR.

Discussion and conclusion: Our findings suggest that polymorphism rs10573247 may contribute to the risk of breast cancer through the functional effect of this polymorphism on miRNA binding.

Keywords: Bioinformatic; Breast Cancer; Deletion polymorphism rs10573247; HMGA2; miR-3125; miR-4476.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Prediction of miRNA binding sites in the 3’ UTR of HMGA2 encompassing polymorphismrs10573247 by the RNA hybrid online tool. A darker boxed line indicates the stronger influence of rs10573247 on the binding site for miR-3125 relative to other miRNAs
Fig. 2
Fig. 2
Enrichment analyses of HMGA2 gene
Fig. 3
Fig. 3
Protein-protein interactions of HMGA2 gene using STRING
Fig. 4
Fig. 4
Electrophoresis visualization of the RFLP-PCR products. The genotype TT/TT displayed two bands, 147 bp and 224 bp (well 2). The heterozygous genotype TT/-- exhibited three bands: 224 bp, 147 bp, and 371 bp (wells 1 and 5). The genotype --/-- showed a single band of 371 bp (wells 3 and 4). L is a 100-bp ladder
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Mansoori B, Mohammadi A, Ditzel HJ, Duijf PH, Khaze V, Gjerstorff MF, Baradaran B. HMGA2 as a critical regulator in cancer development. Genes. 2021;12(2):269. doi: 10.3390/genes12020269. - DOI - PMC - PubMed
    1. Cui T, Leng F. Specific recognition of AT-rich DNA sequences by the mammalian high mobility group protein AT-hook 2: a SELEX study. Biochemistry. 2007;46(45):13059–66. doi: 10.1021/bi701269s. - DOI - PubMed
    1. Ozturk N, Singh I, Mehta A, Braun T, Barreto G. (2014). HMGA proteins as modulators of chromatin structure during transcriptional activation. Front cell Dev Biology, 2, 5. - PMC - PubMed
    1. Xu M, Sharma P, Pan S, Malik S, Roeder RG, Martinez E. Core promoter-selective function of HMGA1 and mediator in Initiator-dependent transcription. Genes Dev. 2011;25(23):2513–24. doi: 10.1101/gad.177360.111. - DOI - PMC - PubMed
    1. Fusco A, Fedele M. Roles of HMGA proteins in cancer. Nat Rev Cancer. 2007;7(12):899–910. doi: 10.1038/nrc2271. - DOI - PubMed

MeSH terms