Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Department of Gynecology and Obstetrics, Xiangya Hospital of Central South University, Changsha, 410008, China.
Cell Death Dis. 2021 Nov 3;12(11):1046. doi: 10.1038/s41419-021-04315-1.
Choriocarcinoma stem-like cells (CSLCs) might be at the origin of choriocarcinoma development associated with drug resistance or relapse. Spalt-like transcription factor 4 (SALL4), which is considered to be a stemness-related gene, can be regulated by miRNAs. In this study, SALL4 result is associated with progression-free survival of choriocarcinoma patients and CSLC's stemness characteristics. In addition, it could be downregulated by miR-497-5p by direct binding. miR-497-5p silencing by hypermethylation promoted malignant CSLC phenotype in vitro and in vivo. Furthermore, increased DNA methyltransferases (DNMTs) by SALL4 upregulation inhibited miR-497-5p expression via hypermethylation promotion. SALL4 appeared to be a key factor in promoting stemness phenotype of choriocarcinoma. Silencing miR-497-5p and SALL4 promotes choriocarcinoma progression and forms a feedback loop with DNMT-mediated epigenetic regulation, playing a crucial role in stemness maintenance in choriocarcinoma.
绒癌干细胞（CSLCs）可能是与耐药或复发相关的绒癌发展的起源。SALL4 是一种被认为与干细胞相关的基因，可受 miRNA 调控。本研究中，SALL4 结果与绒癌患者无进展生存期和 CSLC 干细胞特性相关。此外，SALL4 可通过直接结合被 miR-497-5p 下调。miR-497-5p 通过 hypermethylation 沉默促进了体外和体内恶性 CSLC 表型。此外，SALL4 的上调增加了 DNA 甲基转移酶（DNMTs），通过促进 hypermethylation 抑制了 miR-497-5p 的表达。SALL4 似乎是促进绒癌干细胞表型的关键因素。沉默 miR-497-5p 和 SALL4 促进绒癌进展，并与 DNMT 介导的表观遗传调控形成反馈回路，在绒癌干细胞维持中发挥关键作用。
