Exosomal lnc-0599/miR-124-1介导CAFs促进肝癌侵袭转移的调节机制研究

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Cancer associated fibroblasts (CAFs) in microenvironment plays an important role in therecurrence and metastasis. Our previous work has shown that lnc-0599 is overexpressed in exosome secreted by CAFs through microarray, with the inactivation of miR-124-1 expression in its same region of chromosome, and confirmed that lnc-0599 competed endogenous miR-124-1 and promoted the proliferation and metastasis of HCC cells. The detailed mechanisms are not clear: firstly, whether lnc-0599 is mediated by CAFs exosome? Secondly, what is the mechanism for regulating miR-124-1 generating specific mechanism of biological effects through lnc-0599? Whether is lnc-0599, as a core factor, correlated with clinical features or the prognosis of HCC patients? We propose to further study the regulatory mechanisms on cells, animal models and clinical samples, through plasmid transfection, immunofluorescence, proteomics, etc., to answer the above questions. In a word, we will explore the role of CAFs in microenvironment, regulation and molecular mechanisms, and provide a new theoretical and experimental basis for elucidating the progression of HCC.

肝癌是最常见的恶性肿瘤之一，其微环境中的癌相关成纤维细胞（CAFs）在侵袭转移中发挥重要作用。前期通过芯片筛选发现肝癌CAFs分泌exosome中lnc-0599高表达，伴染色体相同区域的miR-124-1表达失活，并初步证实肝癌细胞中lnc-0599通过内源竞争miR-124-1的作用促进增殖与转移。而其中的详细机制尚待明确：肝癌CAFs是否通过exosome的分泌介导肝癌细胞中lnc-0599的变化？肝癌CAFs及肝癌细胞中lnc-0599调节miR-124-1产生生物学效应的具体机制？体液exosome及组织中lnc-0599和miR-124-1的变化与肝癌的转归是否相关？为此，我们拟在细胞、动物模型及临床样本上深入研究，通过质粒转染、免疫荧光、蛋白组学等方法解答以上科学问题，以揭示微环境中CAFs作用肝癌细胞的方式、调控作用及分子机制，为阐明肝癌进展提供新的理论及实验依据。

肝癌是最常见的恶性肿瘤之一，其微环境中的癌相关成纤维细胞（CAFs）在侵袭转移中发挥重要作用。前期通过芯片筛选发现肝癌CAFs分泌exosome中lnc-0599高表达，伴染色体相同区域的miR-124-1表达失活，并初步证实肝癌细胞中lnc-0599通过内源竞争miR-124-1的作用促进增殖与转移。而其中的详细机制尚待明确：肝癌CAFs是否通过exosome的分泌介导肝癌细胞中lnc-0599的变化？肝癌CAFs及肝癌细胞中lnc-0599调节miR-124-1产生生物学效应的具体机制？体液exosome及组织中lnc-0599和miR-124-1的变化与肝癌的转归是否相关？为此，我们拟在细胞、动物模型及临床样本上深入研究，通过质粒转染、免疫荧光、蛋白组学等方法解答以上科学问题，以揭示微环境中CAFs作用肝癌细胞的方式、调控作用及分子机制，为阐明肝癌进展提供新的理论及实验依据。