SLC1A5 enhances malignant phenotypes through modulating ferroptosis status and immune microenvironment in glioma

作者：Liying Han, Jinpeng Zhou, Leiyang Li, Xun Wu, Yingwu Shi, Wenxing Cui, Shenghao Zhang, Qing Hu, Jin Wang, Hao Bai, Haixiao Liu, Chengxuan Guo, Haiyan Cao, Min Chao, Yaqin Hu, Yueyang Mou, Jiao Yang, Dayun Feng, Liang Wang, Yan Qu · 发表于：Cell Death and Disease · 年份：2022 · DOI：10.1038/s41419-022-05526-w · 被引用次数：91 · 研究领域：Ferroptosis and cancer prognosis、Cancer-related molecular mechanisms research、RNA modifications and cancer

Glioma is the most common type of primary malignant tumor in the central nervous system with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. Ferroptosis is a novel and distinct type of programmed cell death, playing a regulatory role in the progression of tumors. However, the role of ferroptosis or ferroptosis-related genes (FRGs) in glioma progression has not been extensively studied. In our study, a novel ferroptosis-related prognostic model, including 7 genes, was established, in which patients classified into the high-risk group had more immuno-suppressive status and worse prognosis. Among these 7 genes, we screened solute carrier family 1 member 5 (SLC1A5), an FRG, as a possible new target for glioma treatment. Our results showed that the expression of SLC1A5 was significantly upregulated in glioblastoma tissues compared with the low-grade gliomas. In addition, SLC1A5 knockdown could significantly inhibit glioma cell proliferation and invasion, and reduce the sensitivity of ferroptosis via the GPX4-dependent pathway. Furthermore, SLC1A5 was found to be related to immune response and SLC1A5 knockdown decreased the infiltration and M2 polarization of tumor-associated macrophages. Pharmacological inhibition of SLC1A5 by V9302 was confirmed to promote the efficacy of anti-PD-1 therapy. Overall, we developed a novel prognostic model for glioma based on the seven-FRGs signature, which could apply to glioma prognostic and immune s...