HIV相关肺癌（HALC）是研究病毒感染介导的炎症微环境与肿瘤恶性进展的理想人模型。我们的前期工作表明携HIV-1 gp120 DNA的巨噬细胞（BMM-gp120）具类肿瘤相关巨噬细胞表型，其可通过分泌蛋白质向肺癌细胞传递翻译调控信号和exosome蛋白。因此，本项目拟进一步回答BMM-gp120是否可通过exosome调控肺癌细胞的翻译以促进其恶性表型。我们将评价BMM-gp120及其对照BMM-GFP来源的exosome分别对肺癌细胞的翻译中mRNA（RNC-mRNA）的影响，用蛋白质组学研究exosome的差异蛋白质和蛋白转运，预测可能解释HALC病因机制的RNC-mRNA生物学标记物。进而在体外研究这些RNC-mRNA翻译比例改变与exosome蛋白的相关机制，并用动物实验验证这些RNC-mRNA对肿瘤进展的影响。本项目有望首次从肿瘤微环境和翻译组学角度揭示HALC的新病因机制。

HIV-1 associated lung cancer (HLAC) is an ideal human model for viral infection-mediated inflammation and tumor malignant progression. We have shown that HIV-1 gp120 DNA containing macrophages (BMM-gp120) behave similarly to the tumor-associated macrophages. We found BMM-gp120 can transport signals for translational modulation and exosomal proteins to lung cancer cells. Therefore, we propose to further address whether BMM-gp120 can promote malignant phenotypes of lung cancer cells via exosome-relevant translation modulations. We will isolate exosomes from both BMM-gp120 and its control BMM-GFP; as well as using translatomic strategy to evaluate how the two sorts of exosomes affect the translatome of lung cancer cells. Exosomal proteins will then be quantitatively analyzed by proteomics. Furthermore, we will detect the transported exosomal proteins in lung cancer cells by SILAC-based mass spectrometry. Per pathway analysis, we will identify possible translating mRNA (RNC-mRNA) biomarkers that are potentially relevant to HALC development. These target RNC-mRNAs and their mechanistic connections with exosomal proteins of the infected or uninfected macrophages will be validated in vitro. The candidate RNC-mRNAs will be subjected to animal experiments for confirmation. This study possesses a potential to unveil novel etiological mechanism in HALC in terms of tumor microenvironment and functional translatomics.