越来越多的证据表明肿瘤细胞可以通过代谢重编程提高耐药性。表阿霉素化疗可以诱导乳腺癌细胞糖酵解水平增强，抑制糖酵解可显著逆转表阿霉素耐药，但具体机制尚不明确。基于Affymetrix平台测序乳腺癌亲代及耐药细胞中的差异表达基因，我们选择了差异表达较大，且在乳腺癌耐药细胞、细胞系及组织中均高表达的PARP14。预实验提示：沉默PARP14可抑制乳腺癌细胞增殖、凋亡抵抗、表阿霉素耐药和糖酵解，且推测PARP14/LDHA轴是具体的调控机制。本项目在测序筛选差异基因的基础上，将通过细胞水平、体外动物水平及临床标本水平探讨PARP14通过促进乳腺癌细胞糖酵解诱导其表阿霉素耐药的现象及具体机制。本项目的开展有助于为乳腺癌化疗耐药的防治提供新的靶点及理论基础。

Accumulating evidence has shown that metabolic reprogramming could promote drug resistance in cancer cells. After continuous exposure of epirubicin, we established the resistant MCF-7/ADR cells, which exhibited enhanced glycolysis in relative to the parental MCF-7 cells. Inhibtion of glycolysis could effectively reverse the epirubicin resistance; however, the deep mechanisms within enhanced glycolysis and epirubicin resistance in breast cancer (BRCA) cells remain still unkonwn. By high-flux analysis of parental and epirubicin-resistant BRCA cells based on Affymetrix, we identified PARP14, which was overexpressed in BRCA epirubicin-resistant cells, cell lines and samples. Results of our researches showed that knockdown of PARP14 could inhibit cell proliferation, apoptosis resistance, epirubicin resistance and Warburg effects in BRCA. And PARP14/LDHA axis might be responsible for PARP14-triggered BRCA carcinogenesis. Taken together based on the high-flux detection, we will elucidate the mechanisms involved in the influences of PARP14 on BRCA epirubicin resistance via inducing enhanced glycolysis through a series of experiments, including cells in vitro, animals in vivo and BRCA specimens in clinic. Our study will provide a therapeutic target and theoretical basis for prevention and treatment of BRCA chemoresistance.