2026-10-19 東北大学
図1. 本研究の概要：膠芽腫におけるSeP循環利用機構の模式図。
＜関連情報＞
- https://www.tohoku.ac.jp/japanese/2026/10/press20261019-04-selenoprotein.htm
- https://www.sciencedirect.com/science/article/pii/S2213231726004374
LncRNA CCDC152は、膠芽腫におけるセレン依存性酸化還元恒常性を維持する腫瘍関連セレノプロテインPサイクルを調整する LncRNA CCDC152 coordinates a tumor-associated selenoprotein P cycle that sustains selenium-dependent redox homeostasis in glioblastoma
Stephanie Siu, Hiroki Taguchi, Xi Zheng, Hikari Sugiura, Shota Yamashita, Tatsuya Takahashi, Masato Kosuge, Takayuki Kaneko, Misaki Shimizu, Yoshiteru Shimoda, Kota Noritsugu, Kotoko Arisawa, Mika Watanabe, Takashi Toyama, Masayuki Kanamori, Hidenori Endo, Yoshiro Saito
Redox Biology Available online: 12 October 2026
DOI:https://doi.org/10.1016/j.redox.2026.104438
Highlights
- GBM cells establish a SELENOP–LRP8 cycle that reutilizes extracellular selenium.
- CCDC152 coordinates SELENOP production, LRP8 expression, and selenoprotein homeostasis.
- CCDC152 depletion lowers GPX1/GPX4 and increases ferroptosis susceptibility.
- The CCDC152– SELENOP–LRP8 axis represents a redox vulnerability in GBM.
Abstract
Selenium is essential for the synthesis of redox-active selenoproteins, including glutathione peroxidase 4 (GPX4), a central suppressor of ferroptosis. However, how malignant cells coordinate selenium acquisition and reutilization to maintain redox homeostasis remains poorly understood. Here, we identify a tumor-associated selenoprotein P (SELENOP) cycle in glioblastoma (GBM) that is coordinated by the long non-coding RNA (lncRNA) CCDC152. Highly proliferative GBM cells secrete SELENOP, recapture it through LRP8, and reutilize selenium to maintain intracellular selenoprotein abundance and cell proliferation. Disruption of SELENOP or LRP8 suppressed GBM cell proliferation, while LRP8 depletion reduced GPX1 and GPX4 abundance and its intracellular domain was required for growth-promoting activity. Unexpectedly, although CCDC152 suppresses SELENOP translation in hepatocyte-derived cells, it positively regulated SELENOP production, LRP8 expression, and intracellular GPX1 and GPX4 abundance in GBM cells. CCDC152 depletion also increased ferroptosis susceptibility. Clinical analyses further showed that elevated expression of SELENOP and CCDC152 was associated with poor prognosis in astrocytoma, IDH-mutant. Together, these findings identify the CCDC152– SELENOP–LRP8 axis as a tumor-adapted selenium utilization system that couples extracellular selenium transport to intracellular redox homeostasis, revealing selenium utilization as a redox vulnerability that may be exploited by ferroptosis-inducing therapies.
