三阴性乳腺癌（TNBC）恶性程度高，缺乏已知治疗靶点，化疗是其唯一可能有效的系统治疗。申请人前期通过分析近300例TNBC标本全基因转录组信息和化疗疗效，建立了10基因疗效预测模型（含2个长链非编码RNA[lncRNA]）。其中，lncRNA SNRPEP4高表达与化疗耐药显著相关。按预实验，SNRPEP4是SNRPE的假基因，两者的3’UTR序列高度重合。我们推测SNRPEP4可能具有“miRNA生物海绵”效应，通过清除能抑制SNRPE表达的miRNA而发挥作用。我们将研究SNRPEP4和SNRPE对TNBC细胞化疗敏感性的影响；应用ChIRP技术、荧光报告基因实验等确立SNRPEP4、SNRPE和miRNA三者间交互作用；并明确SNRPEP4调控轴的临床价值。本项目将证实SNRPEP4在TNBC化疗耐药中的地位，为精准逆转TNBC化疗抵抗提供新思路。

Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer. Chemotherapy is the current mainstay of treatment for this subtype. We have analyzed about 300 TNBC sample using transcriptome microarrays to predict the chemo-sensitivity of TNBC and successfully developed an integrated mRNA-long noncoding RNAs (lncRNA) signature based on eight mRNAs and two lncRNAs (HIST2H2BC and SNRPEP4). According to the preliminary experiments such as RNA Pull Down assay, SNRPEP4 does not combine with a specific functional protein. Of note, SNRPEP4 is a pseudogene of SNRPE and shares partial 3’ UTR with SNRPE. Therefore, we speculate that SNRPEP4 might works as a “miRNA sponge”, which could eliminate the miRNAs targeting SNRPE. In this project, we would investigate the effect of SNRPEP4 and SNRPE in chemo-sensitivity of TNBC, reveal the interactions between SNRPEP4, SNRPE, and miRNA using ChIRP and luciferase reporter assays, and determine the clinical relevance of SNRPEP4-miRNA-SNRPE regulation axis. The findings from the present project would help to clarify the effect of SNRPEP4 in chemo-resistance and to develop precise and individualized treatment of TNBC patients.