NONHSAT087648/BHLHE40在化疗诱导乳腺癌细胞发生EMT中的机制研究

The mechanism of chemotherapy resistance in breast cancer is complicated. EMT was reported to be involve in the drug resistance in cancer. lncRNAs（long noncoding RNAs）are known as key regulators of tumor metastasis. However, the role of lncRNA in chemotherapy induced EMT in breast cancer cells remain elusive. lncRNA microarray was performed to obtain the differential expressed lncRNAs stimulated by epirubicin treatment. NONHSAT087648 was selected and validated for further study. Bioinformatics analysis suggested that BHLHE40 might be the target gene of NONHSAT087648. We hypothesize that epirubicin induces the EMT of breast cancer through upregulation of BHLHE40 mediated by NONHSAT087648. Further study will be performed to determine the role of NONHSAT087648/BHLHE40 in chemotherapy induced EMT in breast cancer cells. This study will partly address the mechanism of breast cancer recurrence after chemotherapy and build the foundation for further study.

化疗所致肿瘤细胞EMT在肿瘤耐药中发挥重要作用，然而其机制尚不明确。长链非编码RNA（lncRNA）在肿瘤转移复发中扮演重要角色。课题组在临床标本中发现，新辅助化疗可以增加乳腺癌组织EMT相关转录因子的表达。我们通过lncRNA芯片得到表阿霉素致乳腺癌细胞EMT的差异表达谱并选择NONHSAT087648作为研究对象，发现其在间质化的乳腺癌细胞系中明显低表达，此外在ZR-75-1细胞中敲减NONHSAT087648可以显著促进EMT的过程。我们通过生物信息学预测并验证了其靶基因BHLHE40，发现NONHSAT087648有可能通过甲基化调节BHLHE40的表达。本课题将研究NONHSAT087648/ BHLHE40在表阿霉素致乳腺癌细胞EMT过程中的作用，寻找其中的重要靶点，以期将这一过程阻断，提高化疗效果，为乳腺癌化疗后复发转移的预防及治疗提供坚实的理论基础。

化疗所致肿瘤细胞EMT在肿瘤耐药中发挥重要作用，然而其机制尚不明确。长链非编码RNA（lncRNA）在肿瘤转移复发中扮演重要角色。课题组在临床标本中发现，新辅助化疗可以增加乳腺癌组织EMT相关转录因子的表达。我们通过lncRNA芯片得到表阿霉素致乳腺癌细胞EMT的差异表达谱并选择NONHSAT087648作为研究对象，发现其在间质化的乳腺癌细胞系中明显低表达，此外在ZR-75-1细胞中敲减NONHSAT087648可以显著促进EMT的过程。我们通过生物信息学预测并验证了其靶基因BHLHE40，发现NONHSAT087648有可能通过甲基化调节BHLHE40的表达。本课题主要从细胞实验、动物实验及临床标本三个层次对NONHSAT087648及其靶基因BHLHE40在表阿霉素致乳腺癌细胞EMT过程中的作用进行了研究和验证。本课题将为乳腺癌化疗后复发转移的预防及治疗提供坚实的理论基础。