Poli Valeria, Seclì Laura, Avalle Lidia
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Via Nizza 52, 10126 Turin, Italy.
Cancers (Basel). 2020 Mar 17;12(3):708. doi: 10.3390/cancers12030708.
The establishment and spreading of cancer involve the acquirement of many biological functions including resistance to apoptosis, enhanced proliferation and the ability to invade the surrounding tissue, extravasate from the primary site, survive in circulating blood, and finally extravasate and colonize distant organs giving origin to metastatic lesions, the major cause of cancer deaths. Dramatic changes in the expression of protein coding genes due to altered transcription factors activity or to epigenetic modifications orchestrate these events, intertwining with a microRNA regulatory network that is often disrupted in cancer cells. microRNAs-143 and -145 represent puzzling players of this game, with apparently contradictory functions. They were at first classified as tumor suppressive due to their frequently reduced levels in tumors, correlating with cell survival, proliferation, and migration. More recently, pro-oncogenic roles of these microRNAs have been described, challenging their simplistic definition as merely tumor-suppressive. Here we review their known activities in tumors, whether oncogenic or onco-suppressive, and highlight how their expression and functions are strongly dependent on their complex regulation downstream and upstream of cytokines and growth factors, on the cell type of expression and on the specific tumor stage.
癌症的发生与扩散涉及多种生物学功能的获得，包括抗凋亡、增殖增强以及侵袭周围组织、从原发部位渗出、在循环血液中存活，最终渗出并在远处器官定植形成转移灶的能力，而转移灶是癌症死亡的主要原因。由于转录因子活性改变或表观遗传修饰导致的蛋白质编码基因表达的显著变化，协调了这些事件，并与癌细胞中经常被破坏的微小RNA调控网络相互交织。微小RNA-143和-145是这场游戏中令人费解的参与者，具有明显相互矛盾的功能。它们最初因在肿瘤中水平经常降低而被归类为肿瘤抑制因子，这与细胞存活、增殖和迁移相关。最近，这些微小RNA的促癌作用也被描述，这挑战了它们仅仅作为肿瘤抑制因子的简单定义）。在这里，我们综述了它们在肿瘤中的已知活性，无论是致癌还是抑癌，并强调它们的表达和功能如何强烈依赖于细胞因子和生长因子上下游的复杂调控、表达的细胞类型以及特定的肿瘤阶段。 （注：原文括号内部分在逻辑上似乎不太连贯，翻译时尽量忠实于原文表述，但整体内容存在一定费解之处。）
