REX1通过靶向BMP2/6抑制BMP信号通路促进宫颈癌干细胞自我更新的机制研究

批准号:
82003139
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
曾宇婷
依托单位:
学科分类:
肿瘤干细胞
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
曾宇婷
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中文摘要
干细胞分子标志物REX1参与维持多潜能干细胞的自我更新,但REX1是否能够维持宫颈癌干细胞的自我更新及作用机制尚不清楚。我们的前期研究发现REX1在宫颈癌组织中的表达显著高于正常宫颈组织。过度表达REX1促进宫颈癌细胞的干细胞样特性,并促进其体内成瘤能力,缩短小鼠荷瘤生存期。REX1可以上调OCT3/4、SOX2及C-MYC等在宫颈癌中的表达。全转录组测序显示过度表达REX1显著下调BMP2、BMP6及BMP通路下游基因的表达。因此,本项目期望结合染色质免疫共沉淀、DNA pull-down等实验方法,研究:①REX1对宫颈癌细胞干细胞样特性的调节;②REX1通过直接抑制BMP2及BMP6的转录,抑制BMP信号通路的活性,进而促进宫颈癌干细胞自我更新的分子机制。本项目为宫颈癌干细胞靶向治疗提供新的理论依据。
英文摘要
Stem cell molecular marker REX1 is involved in maintaining the self-renewal of pluripotent stem cells, but whether REX1 can maintain the self-renewal of cervical cancer stem cells and its mechanism is unclear. Our previous studies found that the expression of REX1 in cervical cancer tissues was significantly higher than that in normal cervical tissues. Overexpression of REX1 could promote the stem-like properties of cervical cancer cells in vitro, promote their tumorigenicity in vivo, and shorten the tumor-bearing period of mice. REX1 could up-regulate the expression of OCT3/4, SOX2 and C-MYC etc. in cervical cancer. Furthermore, The RNA-sequence results showed that REX1 overexpression significantly down-regulated the expression of BMP2 and BMP6. Therefore,this project hopes to combine Chromatin Immunoprecipitation(ChIP), DNA pull-down and other experimental methods to study: ① the effect of REX1 in stem cell-like characteristics of cervical cancer cells; ② the molecular mechanisms of REX1 in self-renewal of cervical cancer stem cell by directly inhibiting the transcription of BMP2、BMP6 and BMP pathway target genes, and then, inhibiting the activity of BMP signaling pathway. This project provides a new theoretical basis for targeted therapy of cervical cancer stem cells.
期刊论文列表
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专利列表
DOI:10.1016/j.isci.2023.107902
发表时间:2023-10-20
期刊:ISCIENCE
影响因子:5.8
作者:Zeng, Yu-Ting;Liu, Wen-Fang;Zhang, Peng-Sheng;Li, Shan
通讯作者:Li, Shan
REX1 promotes EMT-induced cell metastasis by activating the JAK2/STAT3-signaling pathway by targeting SOCS1 in cervical cancer
REX1 通过靶向宫颈癌中的 SOCS1 激活 JAK2/STAT3 信号通路,促进 EMT 诱导的细胞转移
DOI:10.1038/s41388-019-0906-3
发表时间:2019-10-24
期刊:ONCOGENE
影响因子:8
作者:Zeng, Yu-Ting;Liu, Xiao-Fang;Zheng, Peng-Sheng
通讯作者:Zheng, Peng-Sheng
国内基金
海外基金
