Cupido-Sánchez María Guadalupe, Herrera-González Norma Estela, Mendoza Columba Citlalli Barrera, Hernández María Luisa Morales, Ramón-Gallegos Eva
Molecular Oncology Lab, Escuela Superior de Medicina, Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomás, 11340, Ciudad de México, Mexico.
Environmental Cytopathology Lab, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional. Wilfrido Massieu, Esq. Cda. Manuel Stampa Zacatenco, Gustavo A. Madero, 07736, Ciudad de México, Mexico.
Photodiagnosis Photodyn Ther. 2021 Mar;33:102106. doi: 10.1016/j.pdpdt.2020.102106. Epub 2020 Nov 17.
Breast cancer is the most common malignancy effecting women, and the triple-negative breast cancer (TNBC) subtype is particularly aggressive. This study aimed to evaluate the differential expression pattern of microRNAs (miRNAs) between untreated MDA-MB-231 cells (TNBC cell model) and those that survived photodynamic therapy (PDT) to gain insights into cell survival mechanisms.
Two PDT cycles were applied to MDA-MB-231 cells, using δ-aminolevulinic acid (ALA) followed by laser light at 635 nm. RNA was obtained from cells surviving PDT and untreated cells. The miRNAs expression profile was analyzed to detect the differences between the two groups. The potential target network of hsa-miR-16 was examined in silico with the integrative database Ingenuity® Pathway Analysis software.
After the first and second PDT cycles, 17.8% and 49.6% of the MDA-MB-231 cells were viable. Microarray profiling of miRNAs showed decreased hsa-miR-16 expression (p < 0.05) in MDA-MB-231 cells surviving PDT when compared to the control cells. The predicted downstream targets of hsa-miR-16 were: 1) tumor suppressor protein 53; 2) molecules related to the cell cycle, such as cyclin D1, D3, and E1, and checkpoint kinase 1; 3) cell proliferation molecules, including fibroblast growth factor 1, 2 and 7 and fibroblast growth factor receptor 1; and 4) apoptosis-related molecules, consisting of BCL-2, B-cell leukemia/lymphoma 2, caspase 3, and cytochrome c.
The differential expression of hsa-miR-16 between untreated MDA-MB-231 cells and those surviving PDT has not been previously reported. There was a lower expression of hsa-miR-16 in treated cells, which probably altered its downstream target network. In silico analysis predicted, a network related to the cell cycle, proliferation and apoptosis. These results are congruent with previous descriptions of hsa-miR-16 as a tumor suppressor and suggest that the treated population has increased their capacity to survive.
乳腺癌是影响女性的最常见恶性肿瘤，三阴性乳腺癌（TNBC）亚型尤其具有侵袭性。本研究旨在评估未处理的MDA-MB-231细胞（TNBC细胞模型）与光动力疗法（PDT）后存活的细胞之间微小RNA（miRNA）的差异表达模式，以深入了解细胞存活机制。
对MDA-MB-231细胞进行两个PDT周期，使用δ-氨基乙酰丙酸（ALA），随后用635nm激光照射。从PDT后存活的细胞和未处理的细胞中获取RNA。分析miRNA表达谱以检测两组之间的差异。使用综合数据库Ingenuity® Pathway Analysis软件在计算机上检查hsa-miR-16的潜在靶标网络。
在第一个和第二个PDT周期后，分别有17.8%和49.6%的MDA-MB-231细胞存活。miRNA的微阵列分析显示，与对照细胞相比，PDT后存活的MDA-MB-231细胞中hsa-miR-16表达降低（p < 0.05）。hsa-miR-16的预测下游靶标为：1）肿瘤抑制蛋白53；2）与细胞周期相关的分子，如细胞周期蛋白D1、D3和E1，以及关卡激酶1；3）细胞增殖分子，包括成纤维细胞生长因子1、2和7以及成纤维细胞生长因子受体1；4）凋亡相关分子，包括BCL-2、B细胞白血病/淋巴瘤2、半胱天冬酶3和细胞色素c。
未处理的MDA-MB-231细胞与PDT后存活的细胞之间hsa-miR-16的差异表达此前尚未见报道。处理后的细胞中hsa-miR-16表达较低，这可能改变了其下游靶标网络。计算机分析预测了一个与细胞周期、增殖和凋亡相关的网络。这些结果与之前将hsa-miR-16描述为肿瘤抑制因子的报道一致，并表明处理后的细胞群体存活能力增强。
