Aranza-Martínez Alberto, Sánchez-Pérez Julio, Brito-Elias Luis, López-Camarillo César, Cantú de León David, Pérez-Plasencia Carlos, López-Urrutia Eduardo
Laboratorio de Genómica Funcional, Facultad de Estudios Superiores Iztacala Universidad Nacional Autónoma de México (UNAM), Tlalnepantla, Mexico.
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, Mexico City, Mexico.
Front Oncol. 2021 Nov 4;11:752270. doi: 10.3389/fonc.2021.752270. eCollection 2021.
The resistance that Triple-Negative Breast Cancer (TNBC), the most aggressive breast cancer subtype, develops against radiotherapy is a complex phenomenon involving several regulators of cell metabolism and gene expression; understanding it is the only way to overcome it. We focused this review on the contribution of the two leading classes of regulatory non-coding RNAs, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), against ionizing radiation-based therapies. We found that these regulatory RNAs are mainly associated with DNA damage response, cell death, and cell cycle regulation, although they regulate other processes like cell signaling and metabolism. Several regulatory RNAs regulate multiple pathways simultaneously, such as miR-139-5p, the miR-15 family, and the lncRNA HOTAIR. On the other hand, proteins such as CHK1 and WEE1 are targeted by several regulatory RNAs simultaneously. Interestingly, the study of miRNA/lncRNA/mRNA regulation axes increases, opening new avenues for understanding radioresistance. Many of the miRNAs and lncRNAs that we reviewed here can be used as molecular markers or targeted by upcoming therapeutic options, undoubtedly contributing to a better prognosis for TNBC patients.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，其对放疗产生的抗性是一个复杂的现象，涉及细胞代谢和基因表达的多个调节因子；了解这一现象是克服它的唯一途径。我们将这篇综述聚焦于两类主要的调节性非编码RNA，即微小RNA（miRNA）和长链非编码RNA（lncRNA），对基于电离辐射的治疗方法的作用。我们发现，这些调节性RNA主要与DNA损伤反应、细胞死亡和细胞周期调控相关，尽管它们也调节细胞信号传导和代谢等其他过程。几种调节性RNA同时调节多个途径，如miR-139-5p, miR-15家族和lncRNA HOTAIR。另一方面，CHK1和WEE1等蛋白质同时受到几种调节性RNA的靶向作用。有趣的是，对miRNA/lncRNA/mRNA调节轴的研究不断增加，为理解放射抗性开辟了新途径。我们在此综述的许多miRNA和lncRNA可作为分子标志物，或成为未来治疗方案的靶点，无疑有助于改善TNBC患者的预后。
