Inhibitory effect of calycosin on breast cancer cell progression through downregulating lncRNA HOTAIR and downstream targets:HuR and IGF2BP1  

作　　者：Yuhong Li Hui Miao Wei Wei Jing Tian Jian Chen 

机构地区：[1]Key Laboratory of Tumor Immunology and Microenvironmental Regulation of Guangxi,Guilin Medical University,Guilin 541004,China [2]Chengde Medical University,Chengde 067000,China [3]Department of Physiology,Guilin Medical University,Guilin 541004,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第2期225-236,共12页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the Natural Science Foundation of Guangxi(No.2019GXNSFFA245001);the Innovation Project of Guangxi Graduate Education(No.YCSW2022383)。

摘　　要：Breast cancer is the most commonly diagnosed cancer worldwide.Previously,we reported that calycosin,a typical isoflavone phytoestrogen,triggers apoptosis and is associated with lncRNA HOTAIR in the estrogen receptor(ER)-positive breast cancer MCF-7-cell line.In the present study,we aim to uncover the mechanism of lncRNA HOTAIR in the inhibitory effect induced by calycosin in both ER-positive and ER-negative breast cancer cell lines.Results show that calycosin significantly inhibits proliferation and triggers apoptosis in both ER-positive(MCF-7 and T47D)and ER-negative(MDA-MB-231 and SK-BR-3)breast cancer cell lines,accompanied by downregulation of lncRNA HOTAIR expression.Accordingly,knockdown of lncRNA HOTAIR promotes the anti-tumor effect of calycosin,while overexpression of lncRNA HOTAIR attenuates this effect.Meanwhile,the expression levels of HuR and IGF2BP1 are also reduced by calycosin.More importantly,calycosin facilitates the downregulation of HuR and IGF2BP1 caused by decreasing lncRNA HOTAIR expression,and the upregulation of HuR and IGF2BP1 caused by overexpression of lncRNA HOTAIR is weakened by calycosin.These results demonstrate that downregulating HuR and IGF2BP1 by suppressing lncRNA HOTAIR results in inhibited growth of breast cancer cells by calycosin.In addition,the binding of HuR and IGF2BP1 to lncRNA HOTAIR is detected by RIP assay,implying an interaction between these two proteins and lncRNA HOTAIR.Together,lncRNA HOTAIR may play a carcinogenic role in breast cancer development and has the potential to be a novel therapeutic target for breast cancer in the future,especially in isoflavone phytoestrogen therapy.

关 键 词：lncRNA HOTAIR HUR IGF2BP1 CALYCOSIN breast cancer 

分 类 号：R737.9[医药卫生—肿瘤]