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Published on: May 30, 2012
miR-497-5p/SALL4 axis promotes stemness phenotype of choriocarcinoma and forms a feedback loop with DNMT-mediated
Zheng Peng1, Yi Zhang2, Dazun Shi2
1Department of Gynecology and Obstetrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. pengzheng2019@126.com.
Abstract:
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.
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