Department of Experimental Oncology and Molecular Medicine-Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. delia.mezzanzanica@ istitutotumori.mi.it
Expert Rev Mol Diagn. 2011 Apr;11(3):277-86. doi: 10.1586/erm.11.1.
miRNAs are a class of small non-coding RNAs that regulate the stability or translational efficiency of targeted mRNAs. miRNAs are involved in many cellular processes, such as differentiation, proliferation and apoptosis, which are altered in cancer through miRNA expression dysregulation. In this article we will discuss recent findings implicating miRNAs in apoptotic program regulation using ovarian carcinoma as an example. Ovarian cancer is the most lethal gynecological malignancy. Most patients are diagnosed with advanced disease that is conventionally managed with surgical resection followed by platinum-based chemotherapy. Killing of cancer cells by chemotherapeutic agents or by triggering cell-surface death receptors relies on activation of apoptotic programs executed through receptor-mediated extrinsic pathways and mitochondrial-dependent intrinsic pathways. Despite an initial good response to chemotherapy, ovarian cancer patients typically experience disease relapse within 2 years of the initial treatment developing resistance even to structurally different drugs. Thus, also in this pathology, tumor cells are able to evade apoptosis using multiple mechanisms, several of which are dependent on miRNA gene regulation.
miRNAs 是一类小的非编码 RNA，可调节靶向 mRNAs 的稳定性或翻译效率。miRNAs 参与许多细胞过程，如分化、增殖和凋亡，这些过程在癌症中通过 miRNA 表达失调而改变。在本文中，我们将讨论最近的发现，即 miRNAs 在凋亡程序调节中的作用，以卵巢癌为例。卵巢癌是最致命的妇科恶性肿瘤。大多数患者被诊断为晚期疾病，传统上采用手术切除加铂类化疗进行治疗。化疗药物或通过触发细胞表面死亡受体杀死癌细胞，依赖于通过受体介导的外在途径和线粒体依赖的内在途径执行的凋亡程序的激活。尽管对化疗有最初的良好反应，但卵巢癌患者通常在初始治疗后 2 年内经历疾病复发，即使对结构不同的药物也会产生耐药性。因此，在这种病理中，肿瘤细胞也能够使用多种机制逃避凋亡，其中一些机制依赖于 miRNA 基因的调节。
