MEK4/JNK1通路在调控乳腺癌药物敏感性中发挥重要作用，但具体调控机制仍不明确。课题组发现：乳腺癌耐药细胞中CBR3-AS1、转录因子NRF2及JNK通路关键因子MEK4、JNK1高表达，miR-25-3p低表达；预测发现MEK4、JNK1和CBR3-AS1具有相同的与miR-25-3p结合的MRE序列，CBR3-AS1启动子区具有NRF2结合位点。那么CBR3-AS1是否被NRF2激活参与miR-25-3p双靶向抑制MEK4/JNK1通路，调控乳腺癌药物敏感性？本课题拟在明确CBR3-AS1及MEK4/JNK1与miR-25-3p特异性结合的基础上，比较分别及相互干预CBR3-AS1与miR-25-3p时乳腺癌细胞药物敏感性的改变与MEK4/JNK1水平变化的相关性，考察NRF2对CBR3-AS1的激活作用。阐明NRF2激活CBR3-AS1双靶向调控乳腺癌药物敏感性的作用与分子机制。

MEK4/JNK1 pathway plays an important role in regulating drug sensitivity of breast cancer, but the mechanism is still unclear. Our group found that: CBR3-AS1, transcription factor NRF2 and JNK pathway key factor MEK4, JNK1 were high expressed in drug resistant breast cancer cells and miR-25-3p was low expressed; MEK4, JNK1 and CBR3-AS1 share the same MRE sequence predicted to bind to miR-25-3p, the CBR3-AS1 promoter include 3 NRF2 binding sites. Whether CBR3-AS1 is activated by NRF2 and involved in the double-targeted inhibition of the MEK4/JNK1 pathway by miR-25-3p, regulating drug sensitivity in breast cancer? This study try to figure out whether CBR3-AS1 and MEK4/JNK1 could bind to miR-25-3p, intervention expression of CBR3-AS1 and miR-25-3p both or respectively could change breast cancer cells drug sensitivity, and confirm whether or not MEK4/JNK1 were involved. To elucidate the mechanism of NRF2 activate CBR3-AS1 then regulate breast cancer drug sensitivity.