Title: Isorhapontigenin (ISO) inhibits stem cell-like properties and invasion of bladder cancer cell by attenuating CD44 expression.
Authors: Luo, Yisi; Tian, Zhongxian; Hua, Xiaohui; Huang, Maowen; Xu, Jiheng; Li, Jingxia; Huang, Haishan; Cohen, Mitchell; Huang, Chuanshu
Published In Cell Mol Life Sci, (2020 Jan)
Abstract: Cancer stem cells (CSC) are highly associated with poor prognosis in cancer patients. Our previous studies report that isorhapontigenin (ISO) down-regulates SOX2-mediated cyclin D1 induction and stem-like cell properties in glioma stem-like cells. The present study revealed that ISO could inhibit stem cell-like phenotypes and invasivity of human bladder cancer (BC) by specific attenuation of expression of CD44 but not SOX-2, at both the protein transcription and degradation levels. On one hand, ISO inhibited cd44 mRNA expression through decreases in Sp1 direct binding to its promoter region-binding site, resulting in attenuation of its transcription. On the other hand, ISO also down-regulated USP28 expression, which in turn reduced CD44 protein stability. Further studies showed that ISO treatment induced miR-4295, which specific bound to 3'-UTR activity of usp28 mRNA and inhibited its translation and expression, while miR-4295 induction was mediated by increased Dicer protein to enhance miR-4295 maturation upon ISO treatment. Our results provide the first evidence that ISO has a profound inhibitory effect on human BC stem cell-like phenotypes and invasivity through the mechanisms distinct from those previously noted in glioma stem-like cells.
PubMed ID: 31222373
MeSH Terms: 3' Untranslated Regions/drug effects; Binding Sites/drug effects; Cell Line, Tumor; Cyclin D1/metabolism; Down-Regulation/drug effects; Gene Expression Regulation, Neoplastic/drug effects; Humans; Hyaluronan Receptors/metabolism*; MicroRNAs/metabolism; Neoplastic Stem Cells/drug effects*; Neoplastic Stem Cells/metabolism; Promoter Regions, Genetic/drug effects; RNA, Messenger/metabolism; SOXB1 Transcription Factors/metabolism; Stem Cells; Stilbenes/pharmacology*; Transcription, Genetic/drug effects; Ubiquitin Thiolesterase/metabolism; Urinary Bladder Neoplasms