Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, Sydney, Australia.
Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia.
Cancer Sci. 2020 May;111(5):1805-1817. doi: 10.1111/cas.14350. Epub 2020 Mar 28.
Cancer-associated fibroblasts (CAFs) are the most abundant cell type in the tumor microenvironment and are responsible for producing the desmoplastic reaction that is a poor prognostic factor in ovarian cancer. Long non-coding RNAs (lncRNAs) have been shown to play important roles in cancer. However, very little is known about the role of lncRNAs in the tumor microenvironment. We aimed to identify lncRNAs expressed in ovarian CAFs that were associated with patient survival and used computational approaches to predict their function. Increased expression of 9 lncRNAs and decreased expression of 1 lncRNA in ovarian CAFs were found to be associated with poorer overall survival. A "guilt-by-association" approach was used to predict the function of these lncRNAs. In particular, MIR155HG was predicted to play a role in immune response. Further investigation revealed high MIR155HG expression to be associated with higher infiltrates of immune cell subsets. In conclusion, these data indicate expression on several lncRNAs in CAFs are associated with patient survival and are likely to play an important role in regulating CAF function.
癌症相关成纤维细胞（CAFs）是肿瘤微环境中最丰富的细胞类型，负责产生促结缔组织增生反应，这是卵巢癌预后不良的一个因素。长链非编码 RNA（lncRNA）已被证明在癌症中发挥重要作用。然而，lncRNA 在肿瘤微环境中的作用知之甚少。我们旨在鉴定与患者生存相关的在卵巢 CAFs 中表达的 lncRNAs，并利用计算方法预测其功能。结果发现，卵巢 CAFs 中 9 个 lncRNA 的表达增加和 1 个 lncRNA 的表达降低与总生存期较差相关。采用“关联有罪”的方法预测这些 lncRNA 的功能。特别是，MIR155HG 被预测在免疫反应中发挥作用。进一步的研究表明，MIR155HG 的高表达与免疫细胞亚群浸润的增加有关。总之，这些数据表明 CAFs 中几个 lncRNA 的表达与患者的生存相关，并且可能在调节 CAF 功能方面发挥重要作用。
