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miRNAs as radio-response biomarkers for breast cancer stem cells.
Molecular Oncology ( IF 5.0 ) Pub Date : 2020-02-06 , DOI: 10.1002/1878-0261.12635
Carmen Griñán-Lisón 1, 2 , María Auxiliadora Olivares-Urbano 3 , Gema Jiménez 1, 2, 4 , Elena López-Ruiz 1, 2, 5 , Coral Del Val 6 , Cynthia Morata-Tarifa 1, 2, 7 , José Manuel Entrena 1 , Amanda Rocío González-Ramírez 2, 4 , Houria Boulaiz 1, 2, 8 , Mercedes Zurita Herrera 9 , María Isabel Núñez 1, 2, 3 , Juan Antonio Marchal 1, 2, 8
Affiliation  

In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we studied how IR affects the expression of miRNAs related to stemness in different molecular BC subtypes. Exposition of BC cells to radiation doses of 2, 4, or 6 Gy affected their phenotype, functional characteristics, pluripotency gene expression, and in vivo tumorigenic capacity. This held true for various molecular subtypes of BC cells (classified by ER, PR and HER-2 status), and for BC cells either plated in monolayer, or being in suspension as mammospheres. However, the effect of IR on the expression of eight stemness- and radioresistance-related miRNAs (miR-210, miR-10b, miR-182, miR-142, miR-221, miR-21, miR-93, miR-15b) varied, depending on cell line subpopulation and clinicopathological features of BC patients. Therefore, clinicopathological features and, potentially also, chemotherapy regimen should be both taken into consideration, for determining a potential miRNA signature by liquid biopsy in BC patients treated with RT. Personalized and precision RT dosage regimes could improve the prognosis, treatment, and survival of BC patients.

中文翻译:

miRNAs作为乳腺癌干细胞的放射反应生物标志物。

在乳腺癌(BC)中,癌症干细胞(CSC)的存在与复发,转移和放射抵抗有关。放射治疗(RT)是BC的扩展治疗,但并不总是有效的。CSC具有适当的放射抗性机制,并且一些miRNA参与了细胞对电离辐射(IR)的响应。在这里,我们研究了IR如何影响不同分子BC亚型中与茎相关的miRNA的表达。将BC细胞暴露于2、4、6 Gy辐射剂量会影响其表型,功能特性,多能性基因表达以及体内致瘤能力。对于BC细胞的各种分子亚型(按ER,PR和HER-2状态分类),以及铺在单层或作为乳球悬浮的BC细胞,这都是正确的。然而,红外对8种与干性和放射抗性相关的miRNA(miR-210,miR-10b,miR-182,miR-142,miR-221,miR-21,miR-93,miR-15b)表达的影响取决于BC患者的细胞系亚群和临床病理特征。因此,通过液体活检确定在接受RT治疗的BC患者中潜在的miRNA信号,应同时考虑临床病理特征和化疗方案。个性化和精确的RT剂量方案可以改善BC患者的预后,治疗和生存。潜在地,也应同时考虑化疗方案,以通过液体活检确定RT治疗的BC患者的潜在miRNA信号。个性化和精确的RT剂量方案可以改善BC患者的预后,治疗和生存。潜在地,也应同时考虑化疗方案,以通过液体活检确定RT治疗的BC患者的潜在miRNA信号。个性化和精确的RT剂量方案可以改善BC患者的预后,治疗和生存。
更新日期:2020-01-13
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