长链非编码RNA RP.11-461A8.5：调控乳腺癌耐药的新机制

紫杉醇是乳腺癌化疗的基石，但其诱发的化疗耐药是临床治疗瓶颈。RP.11-461A8.5是我们采用芯片技术筛选获得、差异低表达于乳腺癌耐药细胞中、功能未知的lncRNA。前期研究发现，乳腺癌细胞中抑制RP.11-461A8.5可诱导细胞耐药；生物信息学及实验结果初步确定TRAP1为其下游靶基因；RP.11-461A8.5表达沉默可上调TRAP1表达；而文献报道TRAP1与乳腺癌耐药密切相关，提示RP.11-461A8.5可能通过TRAP1影响乳腺癌耐药性。本课题拟阐明RP.11-461A8.5在乳腺癌中的表达规律；采用过表达和沉默策略，明确RP.11-461A8.5对乳腺癌耐药的影响；以TRAP1为机制线索，揭示RP.11-461A8.5调控乳腺癌耐药的分子机制。RP.11-461A8.5在乳腺癌耐药方面尚无研究报道，研究可能为逆转乳腺癌耐药提供新靶标。

Paclitaxel is the cornerstone of breast cancer chemotherapy, but drug resistance is a difficult problem in the process of chemotherapy. Using lncRNA array technology, we found that RP.11-461A8.5 significantly down-expressed in the MCF-7/PTX cells. We further found that down-regulate of RP.11-461A8.5 in MCF-7 cells can induced MCF-7 cell PTX resistance; we predicted TRAP1 as a potential target gene of RP.11-461A8.5 by employing lncRNA target gene prediction softwares, and we also found that down-regulate RP.11-461A8.5 could up-regulate the expression of TRAP1, which indicated that RP.11-461A8.5might be involved in the drug resistance of breast cancer through TRAP1. In this study, we will further uncover the biology characteristics of RP.11-461A8.5; we want to detect the effect of RP.11-461A8.5 on breast cancer drug resistance through over-expression and down-expression strategy, we use TRAP1 as clue, we want to explore the undergoing molecular mechanism of RP.11-461A8.5 induced breast cancer drug resistance. There was few information about the relationship between lncRNA and breast cancer drug resistance. This study will provide a potential intervention target for reversing the drug resistant for breast cancer therapy.