调控肿瘤相关巨噬细胞功能的lncRNA AC016405.1对乳腺癌转移作用的研究

Tumor associated macrophages are a fundamental part of tumor microenvironments,playing an important role in tumor progression . TAMs develop into alternatively activated or M2-protumor polarized macrophage, not into classically activated or M1-antitumor polarized macrophages. However, the mechanizm of regulation of macrophage polarization is still unknown. Long noncoding RNAs(lncRNA) participate in multiple cellular processes and modulate tumorigenesis and cancer development by interfering with protein expression and function. Our previous findings demonstrated lncRNA AC016405.1 specially expresses in M2 macrophage and regulates macrophage polarization.Our study aims to inhibit M2-protumor polarization via interfering lncRNA expression, restore M1- antitumor polarization. Furthermore,we will investigate the mechanism of differential lncRNA expression and their interaction with inflammatory signaling proteins to regulate macrophage polarization. Our study will shed light on the role of lncRNAs participating in macrophage polarization, and will help to provide novel molecular targets for therapies against tumor inflammatory microenvironments.

肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中具有高度异质性和可塑性的炎症细胞，对乳腺癌转移有重要的促进作用。TAMs表现为促肿瘤的选择性激活（M2）状态，而不表现抑肿瘤的经典性激活（M1）状态，是其促进乳腺癌转移的主要原因。但是，调控TAMs表 型的分子机制目前仍未清楚。长非编码RNA（lncRNA）是调控细胞生物学特性的重要表观遗传学机制。我们预实验发现lncRNA AC016405.1在M2型巨噬细胞中特异性表达升高，并有调控巨噬细胞激活的作用。由此，本项目拟通过干预TAMs中AC016405.1的表达，抑制乳腺癌转移。并进一步揭示不同类型巨噬细胞中lncRNA差异表达的机制，以及lncRNA调控TAMs功能的分子机理。本研究有助阐明lncRNA通过调控TAMs激活促进乳腺癌转移的分子机制，为靶向非可控性炎症肿瘤微环境治疗乳腺癌提供新的分子靶点。

肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中具有高度异质性和可塑性的炎症细胞，对乳腺癌转移有重要的促进作用。我们发现Her2+乳腺癌在靶向治疗后，TAMs的长非编码 RNA(lncRNA)谱出现了明显的变化。而另外我们发现该lncRNA ADCPLA能够调控TAMs中PDL1特异性表达升高，并有抑制肿瘤免疫的作用。由此，本项目通过干预 TAMs 中lncRNA ADCPLA的表达，削弱乳腺癌的免疫抑制。本研究阐明了 lncRNA 通过调控TAMs促进乳腺癌免疫抑制的分子机制，为靶向非可控性炎症肿瘤微环境治疗乳腺癌提供新的分子靶点。