DNA核内分布可作为乳腺癌转移的潜在诊断标志物:基于STORM技术OA

Objective To investigate the correlation between subnuclear DNA distribution and breast cancer metastasis via stochastic optical reconstruction microscopy(STORM).Methods Low metastatic breast cancer MCF7 cells and high metastatic breast cancer MDA-MB-231 cells were selected as the research subjects.On this basis,TGFβ was supplemented to establish a breast cancer metastasis model,whereas breast cancer differentiation models were constructed via treatment with two distinct drug combinations:Tazemetostat/Ipatasertib and Rosiglitazone/PD98059,respectively.The efficacy of model establishment was evaluated by MMP9 expression and wound healing assay.The subnuclear distribution of DNA was analyzed by STORM with fluorescence labeling of histone H3,DNA repair protein OGG1 and dsDNA staining.Results In low metastatic breast cancer MCF7 cells,approximately 60%of DNA was distributed in peripheral region of the cell nucleus,whereas only 35%of DNA was localized in the corresponding area in high metastatic breast cancer MDA-MB-231 cells(P=0.0025).In addition,the distribution of DNA in the breast cancer metastasis model aggregates the center of nucleus(P=0.0102),while the distribution of DNA in the breast cancer differentiation model aggregates towards peripheral region of the cell nucleus(P=0.0005,0.0013).Conclusion This study visualized the subnuclear DNA distribution in breast cancer cells with varying metastatic potentials via STORM,uncovered the intrinsic correlation between subnuclear DNA distribution and breast cancer metastasis,and indicated that this distribution could act as a promising diagnostic indicator for breast cancer metastasis.