LncRNA CCDC152 coordinates a tumor-associated selenoprotein P cycle that sustains selenium-dependent redox homeostasis in glioblastoma.
4 affiliations
- 1Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
- 2Department of Neurosurgery, Graduate School of Medicine, Tohoku University, 1-1 Seiryo Aoba-ku, Sendai, 980-8574, Japan.
- 3Department of Pathology, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-ku, Sendai, Miyagi, 980-0803, Japan.
- 4Laboratory of Molecular Biology and Metabolism, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, Miyagi, 980-8578, Japan. Electronic address: [email protected].
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.
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BibTeX
@article{siu2026lncrna,
title = {{LncRNA CCDC152 coordinates a tumor-associated selenoprotein P cycle that sustains selenium-dependent redox homeostasis in glioblastoma.}},
author = {Stephanie Siu and Hiroki Taguchi and Xi Zheng and Hikari Sugiura and Shota Yamashita and Tatsuya Takahashi and Masato Kosuge and Takayuki Kaneko and Misaki Shimizu and Yoshiteru Shimoda and Kota Noritsugu and Kotoko Arisawa and Mika Watanabe and Takashi Toyama and Masayuki Kanamori and Hidenori Endo and Yoshiro Saito},
journal = {Redox biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104438},
url = {https://europepmc.org/article/MED/42874130},
note = {CC BY},
}
RIS
TY - JOUR
TI - LncRNA CCDC152 coordinates a tumor-associated selenoprotein P cycle that sustains selenium-dependent redox homeostasis in glioblastoma.
AU - Stephanie Siu
AU - Hiroki Taguchi
AU - Xi Zheng
AU - Hikari Sugiura
AU - Shota Yamashita
AU - Tatsuya Takahashi
AU - Masato Kosuge
AU - Takayuki Kaneko
AU - Misaki Shimizu
AU - Yoshiteru Shimoda
AU - Kota Noritsugu
AU - Kotoko Arisawa
AU - Mika Watanabe
AU - Takashi Toyama
AU - Masayuki Kanamori
AU - Hidenori Endo
AU - Yoshiro Saito
PY - 2026
DA - 2026/10/12
JO - Redox biology
DO - 10.1016/j.redox.2026.104438
UR - https://europepmc.org/article/MED/42874130
AB - 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.
SN - 2213-2317
ER -