Wang Yiting, Zhou Yifan, Chen Shangwei, Huang Jianwei, Zhang Chen, Huang Shuping, Pan Yujia, Huang Xiaoyan, Qin Junqi, Lin Shenghua
Laboratory Medical, Guangxi Hospital Division of The First Affiliated Hospital, Sun Yat-sen University, Guangxi, China.
Department of Thoracic Surgery, Guangxi Academy of Medical Sciences and The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi, China.
J Chin Med Assoc. 2025 Sep 3. doi: 10.1097/JCMA.0000000000001286.
Phenylalanyl-TRNA Synthetase Subunit Beta (FARSB) is implicated in the progression of multiple cancers and represents a potential therapeutic target. However, its role in lung adenocarcinoma (LUAD) progression and the immune microenvironment remains poorly understood, warranting further investigation into its regulatory mechanisms.
We conducted bioinformatics analyses to investigate the expression levels of FARSB in LUAD, identify enriched pathways, and assess its correlation with patient prognosis and CD8+ T cell infiltration. Bioinformatics analysis was also employed to explore the transcriptional repression of FARSB by SPI1 and to validate the targeting relationship between SPI1 and FARSB. qRT-PCR was utilized to measure the mRNA expression of FARSB and SPI1, while Western blot was used to detect the expression of FARSB, SPI1, PD-L1, and related signaling pathway proteins. Functional assays were performed, including CCK-8 assay for cell viability, EdU incorporation for cell proliferation, and flow cytometry for apoptosis analysis. CFSE staining was used to analyze CD8+ T cell proliferation, and flow cytometry was used to assess the expression of cytokines IFN-γ, GZMB, and TNF-α.
FARSB expression was significantly upregulated in LUAD tissues and cells, and it inhibited CD8+ T cell infiltration. Mechanistically, FARSB activated the mTOR signaling pathway, enhancing LUAD cell viability, proliferation, and anti-apoptotic capabilities, consequently promoting CD8+ T cell exhaustion. The transcription factor SPI1 repressed FARSB expression, thus inhibiting LUAD progression and promoting CD8+T cell anti-tumor immunity.
SPI1 downregulated FARSB expression through transcriptional repression, thereby blocking the mTOR signaling pathway and suppressing LUAD progression and promoting CD8+T cell anti-tumor immunity.
苯丙氨酰 - tRNA合成酶β亚基（FARSB）与多种癌症的进展有关，是一个潜在的治疗靶点。然而，其在肺腺癌（LUAD）进展和免疫微环境中的作用仍知之甚少，有必要进一步研究其调控机制。
我们进行了生物信息学分析，以研究FARSB在LUAD中的表达水平，确定富集的通路，并评估其与患者预后和CD8 + T细胞浸润的相关性。还采用生物信息学分析来探索SPI1对FARSB的转录抑制作用，并验证SPI1与FARSB之间的靶向关系。使用qRT - PCR测量FARSB和SPI1的mRNA表达，同时使用蛋白质免疫印迹法检测FARSB、SPI1、PD - L1和相关信号通路蛋白的表达。进行了功能实验，包括用于细胞活力的CCK - 8实验、用于细胞增殖的EdU掺入实验以及用于凋亡分析的流式细胞术。使用CFSE染色分析CD8 + T细胞增殖，并使用流式细胞术评估细胞因子IFN - γ、GZMB和TNF - α的表达。
FARSB在LUAD组织和细胞中表达显著上调，并抑制CD8 + T细胞浸润。机制上，FARSB激活mTOR信号通路，增强LUAD细胞活力、增殖和抗凋亡能力，从而促进CD8 + T细胞耗竭。转录因子SPI1抑制FARSB表达，从而抑制LUAD进展并促进CD8 + T细胞抗肿瘤免疫。
SPI1通过转录抑制下调FARSB表达，从而阻断mTOR信号通路，抑制LUAD进展并促进CD8 + T细胞抗肿瘤免疫。
