Terrazzan Anna, Crudele Francesca, Corrà Fabio, Ancona Pietro, Palatini Jeffrey, Bianchi Nicoletta, Volinia Stefano
Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.
Laboratory for Advanced Therapy Technologies (LTTA), University of Ferrara, 44121 Ferrara, Italy.
Noncoding RNA. 2023 May 19;9(3):32. doi: 10.3390/ncrna9030032.
Altered expression of circular RNAs (circRNAs) has previously been investigated in breast cancer. However, little is known about the effects of drugs on their regulation and relationship with the cognate linear transcript (linRNA). We analyzed the dysregulation of both 12 cancer-related circRNAs and their linRNAs in two breast cancer cell lines undergoing various treatments. We selected 14 well-known anticancer agents affecting different cellular pathways and examined their impact. Upon drug exposure circRNA/linRNA expression ratios increased, as a result of the downregulation of linRNA and upregulation of circRNA within the same gene. In this study, we highlighted the relevance of identifying the drug-regulated circ/linRNAs according to their oncogenic or anticancer role. Interestingly, and were increased by several drugs in both cell lines. However, they display opposite effects, circ/linVRK1 favors apoptosis whereas circ/linMAN1A2 stimulates cell migration, and only XL765 did not alter the ratio of other dangerous circ/linRNAs in MCF-7. In MDA-MB-231 cells, AMG511 and GSK1070916 decreased circGFRA1, as a good response to drugs. Furthermore, some circRNAs might be associated with specific mutated pathways, such as the PI3K/AKT in MCF-7 cells with circ/linHIPK3 correlating to cancer progression and drug-resistance, or NHEJ DNA repair pathway in TP-53 mutated MDA-MB-231 cells.
此前已对乳腺癌中环状RNA（circRNA）的表达改变进行过研究。然而，关于药物对其调控的影响以及它们与同源线性转录本（linRNA）的关系，我们却知之甚少。我们分析了在接受各种治疗的两种乳腺癌细胞系中12种与癌症相关的circRNA及其linRNA的失调情况。我们选择了14种影响不同细胞通路的知名抗癌药物，并研究了它们的作用。药物处理后，由于同一基因内linRNA下调和circRNA上调，circRNA/linRNA表达比值增加。在本研究中，我们强调了根据其致癌或抗癌作用来鉴定药物调控的circ/linRNA的相关性。有趣的是，两种细胞系中的几种药物都使 和 增加。然而，它们表现出相反的作用，circ/linVRK1促进细胞凋亡，而circ/linMAN1A2刺激细胞迁移，并且只有XL765没有改变MCF-7中其他危险circ/linRNA的比例。在MDA-MB-231细胞中，AMG511和GSK1070916降低了circGFRA1，这是对药物的良好反应。此外，一些circRNA可能与特定的突变通路相关，例如MCF-7细胞中的PI3K/AKT通路，其中circ/linHIPK3与癌症进展和耐药性相关，或者TP-53突变的MDA-MB-231细胞中的NHEJ DNA修复通路。
