Litwin Monika, Szczepańska-Buda Anna, Piotrowska Aleksandra, Dzięgiel Piotr, Witkiewicz Wojciech
Research and Development Centre, Regional Specialist Hospital in Wrocław, Poland.
Research and Development Centre Novasome Sp. z o.o., 51-423 Wrocław, Poland.
Oncol Lett. 2017 May;13(5):3354-3362. doi: 10.3892/ol.2017.5932. Epub 2017 Mar 28.
Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors. It has been suggested that the PIWI-piRNA complex contributes to cancer development and progression by promoting a stem-like state of cancer cells, or cancer stem cells (CSCs). It has been identified that CSCs represent the cells that have undergone epithelial-mesenchymal transition (EMT) and acquired metastatic capacities. However, the molecular association between the EMT process and the stem-cell state remains unclear. Further extensive characterization of CSCs in individual types of tumors is required to identify specific markers for the heterogeneous population of CSCs and therefore selectively target CSCs. Previous studies indicate a reciprocal regulation between PIWI proteins and a complex signaling network linking markers characterized for CSCs and transcription factors involved in EMT. In the present review, studies of PIWI function are summarized, and the potential involvement of PIWI proteins in cancer development and progression is discussed.
癌症是一种组织学和遗传学上异质性的肿瘤细胞群体，其表现出由表观遗传改变所决定的独特分子特征。先前已证明，与PIWI相互作用RNA（piRNA）形成复合物的P元件诱导的精弱睾丸（PIWI）蛋白参与生殖系细胞的表观遗传调控。最近，在各种类型的肿瘤中已发现，通过导致基因组沉默的异常DNA甲基化，PIWI表达（主要是PIWI样蛋白1和2）重新激活。有人提出，PIWI-piRNA复合物通过促进癌细胞或癌症干细胞（CSC）的干细胞样状态，从而促进癌症的发生和发展。已确定CSC代表经历了上皮-间质转化（EMT）并获得转移能力的细胞。然而，EMT过程与干细胞状态之间的分子关联仍不清楚。需要对个体肿瘤类型中的CSC进行进一步广泛的表征，以识别CSC异质性群体的特异性标志物，从而选择性地靶向CSC。先前的研究表明，PIWI蛋白与一个复杂的信号网络之间存在相互调节，该信号网络将CSC特征性标志物与EMT相关转录因子联系起来。在本综述中，总结了PIWI功能的研究，并讨论了PIWI蛋白在癌症发生和发展中的潜在作用。
