Loren Pía, Saavedra Nicolás, Saavedra Kathleen, De Godoy Torso Nadine, Visacri Marília Berlofa, Moriel Patricia, Salazar Luis A
Center of Molecular Biology and Pharmacogenetics, Scientific and Technological Bioresource Nucleus, Universidad de La Frontera, Temuco, Chile.
School of Medical Sciences, University of Campinas, Campinas, Brazil.
Front Pharmacol. 2022 Apr 4;13:831099. doi: 10.3389/fphar.2022.831099. eCollection 2022.
Cisplatin (DDP) is a well-known anticancer drug used for the treatment of numerous human cancers in solid organs, including bladder, breast, cervical, head and neck squamous cell, ovarian, among others. Its most important mode of action is the DNA-platinum adducts formation, inducing DNA damage response, silencing or activating several genes to induce apoptosis; these mechanisms result in genetics and epigenetics modifications. The ability of DDP to induce tumor cell death is often challenged by the presence of anti-apoptotic regulators, leading to chemoresistance, wherein many patients who have or will develop DDP-resistance. Cancer cells resist the apoptotic effect of chemotherapy, being a problem that severely restricts the successful results of treatment for many human cancers. In the last 30 years, researchers have discovered there are several types of RNAs, and among the most important are non-coding RNAs (ncRNAs), a class of RNAs that are not involved in protein production, but they are implicated in gene expression regulation, and representing the 98% of the human genome non-translated. Some ncRNAs of great interest are long ncRNAs, circular RNAs, and microRNAs (miRs). Accumulating studies reveal that aberrant miRs expression can affect the development of chemotherapy drug resistance, by modulating the expression of relevant target proteins. Thus, identifying molecular mechanisms underlying chemoresistance development is fundamental for setting strategies to improve the prognosis of patients with different types of cancer. Therefore, this review aimed to identify and summarize miRs that modulate chemoresistance in DDP-resistant in the top five deadliest cancer, both and human models.
顺铂（DDP）是一种著名的抗癌药物，用于治疗多种实体器官的人类癌症，包括膀胱癌、乳腺癌、宫颈癌、头颈部鳞状细胞癌、卵巢癌等。其最重要的作用方式是形成DNA-铂加合物，诱导DNA损伤反应，使多个基因沉默或激活以诱导细胞凋亡；这些机制导致基因和表观遗传修饰。DDP诱导肿瘤细胞死亡的能力常常受到抗凋亡调节因子的挑战，从而导致化疗耐药，许多患者已经或将会产生DDP耐药性。癌细胞对化疗的凋亡作用产生抵抗，这一问题严重限制了许多人类癌症治疗的成功结果。在过去30年里，研究人员发现了几种类型的RNA，其中最重要的是非编码RNA（ncRNA），这是一类不参与蛋白质生成，但参与基因表达调控的RNA，占人类基因组非翻译部分的98%。一些备受关注的ncRNA包括长链ncRNA、环状RNA和微小RNA（miRs）。越来越多的研究表明，异常的miRs表达可通过调节相关靶蛋白的表达来影响化疗耐药性的发展。因此，确定化疗耐药性发展的分子机制对于制定改善不同类型癌症患者预后的策略至关重要。因此，本综述旨在识别和总结在最致命的五大癌症的小鼠和人类模型中调节DDP耐药性的miRs。
