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Matrine suppression of self‐renewal was dependent on regulation of LIN28A/Let‐7 pathway in breast cancer stem cells
Author(s) -
Li Xiang,
Liang Ting,
Chen SiSi,
Wang Meng,
Wang Rui,
Li Kai,
Wang JiChang,
Xu ChongWen,
Du Ning,
Qin Sida,
Ren Hong
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29396
Subject(s) - matrine , cancer research , chemistry , stem cell , wnt signaling pathway , carcinogenesis , cisplatin , in vivo , pharmacology , microbiology and biotechnology , biology , signal transduction , biochemistry , chemotherapy , genetics , chromatography , gene
Abstract Matrine, a natural product extracted from the root of Sophora flavescens Ait, was the main chemical ingredient of compounds of Kushen injection, which has been widely used for its remarkable anticancer effects for years. The underlying mechanisms for Matrine regulations of human breast cancer stem cells (BrCSCs) are barely known. LIN28, a well‐characterized suppressor of Let‐7 microRNA biogenesis, playing vital roles in regulations of stem cells’ renewal and tumorigenesis. Here we show that the compounds of Kushen injection derived Matrine could suppress the BrCSCs differentiation and self‐renewal through downregulating the expression of Lin28A, resulting in the inactivation of Wnt pathway through a Let‐7b‐dependent way. In opposite to Matrine, Cisplatin treatment increases the ability of tumorsphere formation and the expression of BrCSCs markers, which was partially blocked by either Let‐7b overexpression or CCND1 inhibition. Furthermore, Matrine sensitized BrCSCs to cisplatin's suppression of cancer expansion in vitro and in vivo. Our study uncovers the role of the LIN28A/Let‐7 in BrCSCs renewal, and more importantly, elucidated a novel mechanism by which Matrine induces breast cancer involution.