Zhao Hongbo, Wu Lanxiang, Wu Jing, Yu Huandi, Zhou Jiayi, Luan Baoxin, Xu Congjian
1 Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital and Institute of Obstetrics and Gynecology, Fudan University, Shanghai, China.
2 Institute of Life Sciences, Chongqing Medical University, Chongqing, China.
Reprod Sci. 2018 Mar;25(3):435-442. doi: 10.1177/1933719117715130. Epub 2017 Jun 22.
Sal-like protein 4 (SALL4) has been proved to play a pivotal role in the development and progression of various cancers. Previous studies showed that SALL4 was highly expressed in human choriocarcinoma tissues. However, the role of SALL4 in the biological behavior of human choriocarcinoma cells remains largely unknown. In this study, we first elucidated that SALL4 was highly expressed in human choriocarcinoma cell line JEG-3 and JAR. Sal-like protein 4 knockdown by small interfering RNA (siRNA) decreased c-Myc expression, whereas SALL4 overexpression by transfection of human pLenti-SALL4 construct promoted c-Myc expression. Further data showed that SALL4 overexpression improved cell proliferation of JEG-3 cells, which can be abrogated by c-Myc siRNA. Moreover, our data showed that SALL4 interact with β-catenin and SALL4 overexpression promoted the localization of β-catenin in the nucleus and β-catenin siRNA abrogated SALL4-induced c-Myc expression in JEG-3 cells. These data indicate that aberrantly expressed SALL4 in human choriocarcinoma cells may promote cell proliferation via β-catenin/c-Myc pathway, indicating that SALL4 may be potential treatment targets of human choriocarcinoma.
锌指蛋白4（SALL4）已被证明在多种癌症的发生和发展中起关键作用。先前的研究表明，SALL4在人绒毛膜癌组织中高表达。然而，SALL4在人绒毛膜癌细胞生物学行为中的作用仍不清楚。在本研究中，我们首先阐明SALL4在人绒毛膜癌细胞系JEG-3和JAR中高表达。通过小分子干扰RNA（siRNA）敲低SALL4可降低c-Myc的表达，而转染人pLenti-SALL4构建体过表达SALL4则促进c-Myc的表达。进一步的数据表明，SALL4过表达可促进JEG-3细胞的增殖，而c-Myc siRNA可消除这种促进作用。此外，我们的数据显示SALL4与β-连环蛋白相互作用，SALL4过表达促进β-连环蛋白在细胞核中的定位，而β-连环蛋白siRNA可消除SALL4诱导的JEG-3细胞中c-Myc的表达。这些数据表明，人绒毛膜癌细胞中异常表达的SALL4可能通过β-连环蛋白/c-Myc途径促进细胞增殖，提示SALL4可能是人绒毛膜癌潜在的治疗靶点。
