肿瘤复发是患者死亡主因，肿瘤干细胞（CSC）是导致肿瘤转移、耐药、复发的根本。前期采用芯片、蛋白组学技术发现乳腺癌CSC(BCSC)存在能量代谢和干性相关的LncRNA、蛋白异常，生物信息分析揭示3个新LncRNA与BCSC能量代谢、干性维持密切。干预其中一个LncRNA表达，改变BCSC代谢与干性特征，增强药物敏感性。故推测这些LncRNA通过调控BCSC能量代谢转变，对BCSC富集、干性维持和耐药发挥重要作用。该申请项目拟进一步采用siRNA干扰、RIP-Seq、LC-MS/MS等手段，研究这些LncRNA对BCSC糖酵解、OXPHOS活性，mammospheres形成及药物耐受变化；寻找LncRNA通过靶基因、或互作蛋白，影响下游相关信号途径，调控BCSC能量代谢、CSC干性维持的潜在分子机制。研究结果对深入了解BCSC的能量代谢变化与干性维持、药物耐受，具重要理论与临床价值。

Tumor recurrence is the major cause of death for patients with tumor. Cancer stem cells (CSC) play a critical role on tumor metastasis, drug resistance and recurrence. Our previous studies indicated that aberrant LncRNAs are in breast CSC (BCSC). Three new LncRNAs identified using bioinformation assay have been experimentally proved to involve in energy metabolism and stemness maintenance of BCSC. Interfering one of LncRNAs led to energy metabolism changes and decreased stemness of BCSC. Thus, it raises an interesting question that these novel LncRNAs may play roles in EMR of BCSC, and strengthen generation and stemness maintenance of BCSC. To further verify this hypotheses, we try to study the mechanism of these LncRNAs regulating glucolysis, OXPHOS activity, stemness maintenance, and drug resistance of BCSC using bioinformatics, siRNA, RIP-Seq, and LC-MS/MS to unveil their down-stream targets, interacting proteins and downstream signaling pathway. The results of the study will have essential scientific and clinical value for understanding the EMR, characteristics and differentiation of BCSC, and its drug resistance.