Xu Junfei, Wang Feiran, Wang Xi, He Zhixian, Zhu Xinguo
Department of General Surgery, First Affiliated Hospital, Soochow University, Suzhou, People's Republic of China,
Department of General Surgery, Affiliated Hospital, Nantong University, Nantong, People's Republic of China.
Onco Targets Ther. 2018 Aug 21;11:5075-5082. doi: 10.2147/OTT.S161316. eCollection 2018.
BACKGROUND/PURPOSE: Given the emerging role of microRNA (miRNA) in cancer progression, we investigated the role and mechanism of miRNA-543 (miR-543) in gastric cancer (GC).
Real-time quantitative polymerase chain reaction was conducted to quantify the expression of miR-543. Luciferase reporter assay was used to confirm the association between speckle-type POZ protein (SPOP) and 3'-UTR. Moreover, the role of miR-543 and SPOP in GC was detected using transwell assays. In addition, we investigated the function of miR-543 in the epithelial-mesenchymal transition (EMT) progression.
miR-543 was upregulated in GC. We identified SPOP as a direct target of miR-543, revealing its expression to be inversely correlated with miR-543 expression in GC tissues. Moreover, restoration of SPOP could inhibit miR-543-induced GC cell migration and invasion, whereas downregulation of miR-543 inhibited cell migration and invasion, which was partly abrogated by SPOP knockdown. Furthermore, our data also showed that miR-543 induced EMT of GC cells.
Our results demonstrated that miR-543 functions as a crucial oncogenic miRNA in GC. It exerts strong tumor-promoting effects through targeting SPOP in GC cell migration and invasion.
背景/目的:鉴于微小RNA(miRNA)在癌症进展中日益凸显的作用,我们研究了miRNA - 543(miR - 543)在胃癌(GC)中的作用及机制。
采用实时定量聚合酶链反应来定量miR - 543的表达。荧光素酶报告基因检测用于确认斑点型POZ蛋白(SPOP)与3' - 非翻译区之间的关联。此外,通过Transwell实验检测miR - 543和SPOP在胃癌中的作用。另外,我们研究了miR - 543在上皮 - 间质转化(EMT)进程中的功能。
miR - 543在胃癌中表达上调。我们确定SPOP是miR - 543的直接靶点,发现其在胃癌组织中的表达与miR - 543的表达呈负相关。此外,恢复SPOP可抑制miR - 543诱导的胃癌细胞迁移和侵袭,而miR - 543的下调则抑制细胞迁移和侵袭,敲低SPOP可部分消除这种抑制作用。此外,我们的数据还表明miR - 543可诱导胃癌细胞发生EMT。
我们的结果表明,miR - 543在胃癌中作为一种关键的致癌miRNA发挥作用。它通过靶向SPOP在胃癌细胞迁移和侵袭中发挥强大的促肿瘤作用。