Department of Thoracic-cardiac Surgery, Hubei Provincial Hospital of Traditional Chinese Medicine, Affiliated Hospital of Hubei University of Chinese Medicine, Wuhan, Hubei 430061, China.
Hubei University of Chinese Medicine, Wuhan, Hubei 430061, China.
Immunobiology. 2022 May;227(3):152206. doi: 10.1016/j.imbio.2022.152206. Epub 2022 Mar 15.
Tumor microenvironment (TME) regulated the development of the Lung squamous cell carcinoma (LUSC). To know more about the LUSC, this study tried to figure the role of fscin actin-bundling protein 1 (FSCN1) in the TME. We identified the FSCN1 as the hub immune gene in LUSC, with the use of weighted gene co-expression network analysis (WGCNA) and the Human Protein Atlas. Furthermore, we verified the higher expression of FSCN1 in LUSC compared with the normal tissues by quantitative reverse transcription PCR (qRT-PCR) and immunohistochemistry. We then explored the associations among FSCN1, immune infiltrations, and inflammatory factors with the use of Gene Expression Profiling Interactive Analysis (GEPIA) and Tumor IMmune Estimation Resource (TIMER). As a result, the expressions of FSCN1 was negatively related to the immune infiltrations, and positively related to the expressions of IL1A, IL1B, TGFB1 and TGFA. Moreover, we used the single-cell RNA-sequencing (scRNA-seq) data of LUSC to figure out the expressions level of FSCN1, IL1A, IL1B, TGFB1 and TGFA in the different cell type's of the TME. Finally, through the cytological experiments, we found that FSCN1 affected by TGFB1 contributes to the proliferation, anti-apoptotic effect, migration and invasion of the LUSC cells. In summary, this study Identified FSCN1 as the potential therapeutic target of LUSC, and reveals a complicated immune and inflammatory net in the TME.
肿瘤微环境(TME)调节肺鳞状细胞癌(LUSC)的发展。为了更深入地了解 LUSC,本研究试图探讨 fscin 肌动蛋白束蛋白 1(FSCN1)在 TME 中的作用。我们通过加权基因共表达网络分析(WGCNA)和人类蛋白质图谱确定 FSCN1 是 LUSC 的枢纽免疫基因。此外,我们通过定量逆转录 PCR(qRT-PCR)和免疫组织化学验证了 FSCN1 在 LUSC 中的表达高于正常组织。然后,我们使用基因表达谱交互式分析(GEPIA)和肿瘤免疫估计资源(TIMER)探索 FSCN1 与免疫浸润和炎症因子之间的关系。结果表明,FSCN1 的表达与免疫浸润呈负相关,与 IL1A、IL1B、TGFB1 和 TGFA 的表达呈正相关。此外,我们使用 LUSC 的单细胞 RNA 测序(scRNA-seq)数据,在 TME 的不同细胞类型中确定了 FSCN1、IL1A、IL1B、TGFB1 和 TGFA 的表达水平。最后,通过细胞学实验,我们发现受 TGFB1 影响的 FSCN1 有助于 LUSC 细胞的增殖、抗凋亡作用、迁移和侵袭。总之,本研究鉴定 FSCN1 为 LUSC 的潜在治疗靶点,并揭示了 TME 中复杂的免疫和炎症网络。