Retamales-Ortega Rocío, Oróstica Lorena, Vera Carolina, Cuevas Paula, Hernández Andrea, Hurtado Iván, Vega Margarita, Romero Carmen
Laboratory of Endocrinology and Reproductive Biology, Clinical Hospital University of Chile, Santiago 8380456, Chile.
Department of Obstetrics and Gynecology, Clinical Hospital, Faculty of Medicine, University of Chile, Santiago 8380456, Chile.
Int J Mol Sci. 2017 Feb 26;18(3):507. doi: 10.3390/ijms18030507.
Ovarian cancer is the eighth most common cancer in women worldwide, and epithelial ovarian cancer (EOC) represents 90% of cases. Nerve growth factor (NGF) and its high affinity receptor tyrosine kinase A receptor (TRKA) have been associated with the development of several types of cancer, including EOC; both NGF and TRKA levels are elevated in this pathology. EOC presents high angiogenesis and several molecules have been reported to induce this process. NGF increases angiogenesis through its TRKA receptor on endothelial cells, and by indirectly inducing vascular endothelial growth factor expression. Other molecules controlled by NGF include ciclooxigenase-2, disintegrin and metalloproteinase domain-containing protein 17 (ADAM17) and calreticulin (CRT), proteins involved in crucial processes needed for EOC progression. These molecules could be modified through microRNA regulation, which could be regulated by NGF. MicroRNAs are the widest family of non-coding RNAs; they bind to 3'-UTR of mRNAs to inhibit their translation, to deadenilate or to degraded them. In EOC, a deregulation in microRNA expression has been described, including alterations of miR-200 family, cluster-17-92, and miR-23b, among others. Since the NGF-microRNA relationship in pathologies has not been studied, this review proposes that some microRNAs could be associated with NGF/TRKA activation, modifying protein levels needed for EOC progression.
卵巢癌是全球女性中第八大常见癌症,上皮性卵巢癌(EOC)占病例的90%。神经生长因子(NGF)及其高亲和力受体酪氨酸激酶A受体(TRKA)与包括EOC在内的几种癌症的发生发展有关;在这种病理状态下,NGF和TRKA水平均升高。EOC具有高血管生成活性,并且有几种分子被报道可诱导这一过程。NGF通过其在内皮细胞上的TRKA受体增加血管生成,并间接诱导血管内皮生长因子的表达。受NGF调控的其他分子包括环氧化酶-2、含解整合素和金属蛋白酶结构域蛋白17(ADAM17)和钙网蛋白(CRT),这些蛋白参与了EOC进展所需的关键过程。这些分子可通过微小RNA调控进行修饰,而微小RNA调控可能受NGF调节。微小RNA是最大的非编码RNA家族;它们与mRNA的3'-UTR结合以抑制其翻译、使其去腺苷酸化或降解它们。在EOC中,已描述了微小RNA表达失调,包括miR-200家族、17-92簇和miR-23b等的改变。由于尚未研究病理状态下NGF与微小RNA的关系,本综述提出一些微小RNA可能与NGF/TRKA激活相关,从而改变EOC进展所需的蛋白水平。