Self-assembled DNA nanostructure containing oncogenic miRNA-mediated cell proliferation by downregulation of FOXO1 expression

BMC Cancer

Research

Sandip K. Mishra¹  Avishek Kar²  Umakanta Subudhi²  Kanchan Kumari³ 

[1] Cancer Biology Laboratory, Institute of Life Sciences, 751023, Bhubaneswar, India;DNA Nanotechnology and Application Laboratory, CSIR-Institute of Minerals and Materials Technology, 751013, Bhubaneswar, India;Academy of Scientific and Innovative Research (AcSIR), 201002, Ghaziabad, Uttar Pradesh, India;DNA Nanotechnology and Application Laboratory, CSIR-Institute of Minerals and Materials Technology, 751013, Bhubaneswar, India;Department of Molecular Biology, Umea University, Umea, Sweden;

关键词: DNA nanostructure;    FOXO1;    miRNAs;    Breast cancer;    MCF7 cell line;    P21;    P27;   

DOI  :  10.1186/s12885-022-10423-8

 received in 2022-07-23, accepted in 2022-12-07,  发布年份 2022

来源: Springer

【 摘 要 】

FOXO1 transcription factor not only limits the cell cycle progression but also promotes cell death as a tumor suppressor protein. Though the expression of FOXO1 is largely examined in breast cancer, the regulation of FOXO1 by miRNA is yet to be explored. In the current study, self-assembled branched DNA (bDNA) nanostructures containing oncogenic miRNAs were designed and transfected to the MCF7 cell line to decipher the FOXO1 expression. bDNA containing oncogenic miRNAs 27a, 96, and 182 synergistically downregulate the expression of FOXO1 in MCF7 cells. The down-regulation is evident both in mRNA and protein levels suggesting that bDNA having miRNA sequences can selectively bind to mRNA and inhibit translation. Secondly, the downstream gene expression of p21 and p27 was also significantly downregulated in presence of miR-bDNA nanostructures. The cell proliferation activity was progressively increased in presence of miR-bDNA nanostructures which confirms the reduced tumor suppression activity of FOXO1 and the downstream gene expression. This finding can be explored to design novel bDNA structures which can downregulate the tumor suppressor proteins in normal cells and induce cell proliferation activity to identify early-phase markers of cancer.

【 授权许可】

CC BY   
© The Author(s) 2022

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