LncRNA介导肿瘤相关巨噬细胞促进乳腺癌转移分子机制研究

项目名称： LncRNA介导肿瘤相关巨噬细胞促进乳腺癌转移分子机制研究

项目编号： No.81502302

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 曾银朵

作者单位： 中山大学

项目金额： 18万元

中文摘要： 肿瘤相关巨噬细胞（TAMs）在乳腺癌转移过程中发挥重要作用。前期研究提示TAMs通过分泌CCL18影响乳腺癌的发展和转移，干扰CCL18的表达可显著抑制乳腺癌细胞转移。长链非编码RNA（lncRNA）与肿瘤侵袭转移密切相关。但lncRNA在TAMs促进乳腺癌转移过程中的作用及其分子机制尚未明确。预实验中发现，CCL18作用后的不同乳腺癌细胞中lncRNA表达谱发生显著变化， lncRNA TCONS_00009927在高转移乳腺癌细胞株中高表达，抑制其表达降低乳腺癌细胞侵袭能力，但其分子机制有待阐明。我们假设TAMs调控乳腺癌转移过程中lncRNA TCONS_00009927起着重要作用。本课题利用qRT-PCR、Western blot等进一步探讨lncRNA在介导TAMs促进乳腺癌转移过程中的地位和寻找其下游靶基因，为靶向肿瘤微环境抑制乳腺癌转移寻找新靶点。

中文关键词： 乳腺癌；肿瘤相关巨噬细胞；长链非编码RNA；转移

英文摘要： Tumor-associated macrophages (TAMs) promote breast cancer metastasis. Our previous studies suggested that CCL18 from TAMs influenced breast cancer progression and metastasis, and showed that inhibition of CCL18 with anti-CCL18 antibody or CCL18-siRNA remarkably reduced cancer metastasis. Long noncoding RNA (lncRNA) is associated with tumor metastasis. However, the relationship between TAMs and lncRNA remains unclear. We used microarray analysis to compare lncRNA expression levels between CCL18 treated and untreated breast cancer cell lines. We found that 18 upregulated lncRNAs were enriched in both MCF-7 and BT-474 cell lines. We identified the lncRNA TCONS_00009927 was significantly upregulated in high metastasis potential breast cancer cell lines, but relative molecular mechanism still remains to be clarified. We make a hypothesis that lncRNA TCONS_00009927 acts as a key role in the TAM-mediated invasion-metastasis cascade.The aim is to further define the role of lncRNA TCONS_00009927 in human breast cancer using qRT-PCR, Western blot etc, explore target genes, and provide some effective targets for anti-metastasis therapies.

英文关键词： Breast Cancer;Tumor-associated Macrophages;LncRNA;Metastasis