Du Wei, Ouyang Yuqing, Feng Xiaofan, Yu Chunyan, Zhang Haoke, Chen Siqi, Liu Zixuan, Wang Bo, Li Xueying, Liu Zihe, Deng Weimin
Tianjin Institute of Immunology, Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Tianjin Medical University, Tianjin, 300070, China.
Tianjin Institute of Immunology, Department of Immunology, Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Diseases and Microenvironment of Ministry of Education of China, Tianjin Medical University, Tianjin, 300070, China.
Pulm Pharmacol Ther. 2025 Mar;88:102344. doi: 10.1016/j.pupt.2025.102344. Epub 2025 Jan 30.
Metabolic reprogramming in tumor cells plays a crucial role in promoting cell proliferation and metastasis, and is currently recognized as a significant marker of tumor progression. Interleukin-10 receptor subunit alpha (IL-10RA), a member of the type II cytokine receptor family, is predominantly expressed on macrophages and T cells and plays a crucial role in regulating immune cell metabolism and immune response. However, its role in the energy metabolic pathways of tumor cells remains unclear. In this study, we found increased expression of IL-10RA in human non-small cell lung cancer (NSCLC), and a correlation between increased IL-10RA expression and tumor stage, tumor size, and short overall survival of patients with NSCLC. IL-10RA overexpression significantly promoted the proliferation of NSCLC cell lines and enhanced glycolysis and fatty acid oxidation (FAO), thereby boosting energy production. Correspondingly, the downregulation of IL-10RA inhibited proliferation, glycolysis, and FAO in NSCLC cell lines. Bioinformatic analyses indicated that IL-10RA upregulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. STAT3 inhibitor effectively blocked the increase in FAO levels and cell proliferation induced by IL-10RA overexpression. These findings suggest that IL-10RA accelerates NSCLC cell proliferation by increasing FAO levels via the STAT3 pathway, highlighting IL-10RA as a potential therapeutic target for NSCLC.
肿瘤细胞中的代谢重编程在促进细胞增殖和转移方面起着关键作用，目前被认为是肿瘤进展的重要标志物。白细胞介素-10受体α亚基（IL-10RA）是II型细胞因子受体家族的成员，主要在巨噬细胞和T细胞上表达，在调节免疫细胞代谢和免疫反应中起关键作用。然而，其在肿瘤细胞能量代谢途径中的作用仍不清楚。在本研究中，我们发现IL-10RA在人非小细胞肺癌（NSCLC）中表达增加，且IL-10RA表达增加与NSCLC患者的肿瘤分期、肿瘤大小及较短的总生存期相关。IL-10RA过表达显著促进NSCLC细胞系的增殖，并增强糖酵解和脂肪酸氧化（FAO），从而提高能量产生。相应地，IL-10RA的下调抑制了NSCLC细胞系的增殖、糖酵解和FAO。生物信息学分析表明，IL-10RA上调信号转导和转录激活因子3（STAT3）信号通路。STAT3抑制剂有效地阻断了IL-10RA过表达诱导的FAO水平升高和细胞增殖。这些发现表明，IL-10RA通过STAT3途径增加FAO水平来加速NSCLC细胞增殖，突出了IL-10RA作为NSCLC潜在治疗靶点的地位。
