Gomes Bruno Costa, Rueff José, Rodrigues António Sebastião
Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana 6, Edificio CEDOC II, Room 2.22-2.23, Lisbon, 1150-008, Portugal.
Methods Mol Biol. 2016;1395:137-62. doi: 10.1007/978-1-4939-3347-1_9.
The discovery of small regulatory noncoding RNAs revolutionized our thinking on gene regulation. The class of microRNAs (miRs), a group of small noncoding RNAs (20-22 nt in length) that bind imperfectly to the 3'-untranslated region of target mRNA, has been insistently implicated in several pathological conditions including cancer. Indeed, major hallmarks of cancer, such as cell differentiation, cell proliferation, cell cycle, cell survival, and cell invasion, has been described as being regulated by miRs. Recent studies have also implicated miRs in cancer drug resistance. Regardless of the several studies done until now, drug resistance still is a burden for cancer therapy and patients' outcome, often resulting in more aggressive tumors that tend to metastasize to distant organs. Hence, with this review, we aim to summarize the miRs that influence molecular pathways that are involved in cancer drug resistance, such as drug metabolism, drug influx/efflux, DNA damage response (DDR), epithelial-to-mesenchymal transition (EMT), and cancer stem cells.
小调节性非编码RNA的发现彻底改变了我们对基因调控的看法。微小RNA(miR)类,即一组长度为20-22个核苷酸的小非编码RNA,它们与靶mRNA的3'-非翻译区不完全结合,一直被认为与包括癌症在内的多种病理状况有关。事实上,癌症的主要特征,如细胞分化、细胞增殖、细胞周期、细胞存活和细胞侵袭,都被描述为由miR调控。最近的研究还表明miR与癌症耐药性有关。尽管到目前为止已经进行了多项研究,但耐药性仍然是癌症治疗和患者预后的负担,常常导致更具侵袭性的肿瘤,这些肿瘤往往会转移到远处器官。因此,通过本综述,我们旨在总结影响参与癌症耐药性的分子途径的miR,如药物代谢、药物流入/流出、DNA损伤反应(DDR)、上皮-间质转化(EMT)和癌症干细胞。