Translational cancer research · 2026
The atypical kinase right open reading frame kinase 1 suppresses glioma cell growth through mammalian target of rapamycin inhibition and apoptotic signaling activation.
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Ji Daofei, Li Jicheng, Wang Peng, Gao Shangfeng, Li Wen
Аннотация
BACKGROUND: Gliomas account for the most frequent malignant neoplasms in the central nervous system (CNS). Though there have been developments in therapeutic approaches, the survival rate for most patients remains poor. This research aimed to explore the clinical importance and underlying mechanism of the atypical kinase right open reading frame kinase 1 (RIOK1) in the growth and proliferation of gliomas.
METHODS: Differential expression analysis and survival analysis were assessed in public glioma datasets. The levels of RIOK1 protein expression in glioma tissues and non-tumor brain tissues were assessed via Western blot and immunohistochemical analysis. Cell Counting Kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were employed to evaluate glioma cell proliferation. Living cell imaging technology was applied to explore the impact of RIOK1 upregulation on glioma cell proliferative capacity under hypoxic conditions. Protein levels of selected protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathway and apoptosis-related signaling members were evaluated using Western blot. Finally, glioma xenograft models were established to investigate the effect of RIOK1 on glioma tumorigenesis in vivo.
RESULTS: We observed a significant downregulation of RIOK1 in isocitrate dehydrogenase (IDH) wild-type gliomas relative to IDH mutant-type gliomas. Compared to non-tumor brain tissues, glioma tissues exhibited a significant reduction in RIOK1 expression levels. Furthermore, overexpression of RIOK1 curbed the growth and proliferation of glioma cells, while downregulation of RIOK1 showed the opposite role. Hypoxia induced decreased expression of RIOK1, which was accompanied by elevated expression of hypoxia-inducible factor 1α (HIF-1α). Under hypoxic conditions, overexpression of RIOK1 inhibited the growth of glioma cells as well. Mechanistically, overexpression of RIOK1 diminished mTOR signaling pathway activity while boosting the activity of apoptosis-related signaling. In vivo, RIOK1 downregulation promotes glioma growth.
CONCLUSIONS: RIOK1 expression is lower in glioma tissues than in non-tumor brain tissues, and is particularly lower in IDH wild-type gliomas. RIOK1 functions as a suppressor of glioma cell survival and proliferation, possibly through mTOR pathway inhibition and apoptotic pathway activation.
METHODS: Differential expression analysis and survival analysis were assessed in public glioma datasets. The levels of RIOK1 protein expression in glioma tissues and non-tumor brain tissues were assessed via Western blot and immunohistochemical analysis. Cell Counting Kit-8 (CCK8) and 5-ethynyl-2'-deoxyuridine (EdU) assays were employed to evaluate glioma cell proliferation. Living cell imaging technology was applied to explore the impact of RIOK1 upregulation on glioma cell proliferative capacity under hypoxic conditions. Protein levels of selected protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathway and apoptosis-related signaling members were evaluated using Western blot. Finally, glioma xenograft models were established to investigate the effect of RIOK1 on glioma tumorigenesis in vivo.
RESULTS: We observed a significant downregulation of RIOK1 in isocitrate dehydrogenase (IDH) wild-type gliomas relative to IDH mutant-type gliomas. Compared to non-tumor brain tissues, glioma tissues exhibited a significant reduction in RIOK1 expression levels. Furthermore, overexpression of RIOK1 curbed the growth and proliferation of glioma cells, while downregulation of RIOK1 showed the opposite role. Hypoxia induced decreased expression of RIOK1, which was accompanied by elevated expression of hypoxia-inducible factor 1α (HIF-1α). Under hypoxic conditions, overexpression of RIOK1 inhibited the growth of glioma cells as well. Mechanistically, overexpression of RIOK1 diminished mTOR signaling pathway activity while boosting the activity of apoptosis-related signaling. In vivo, RIOK1 downregulation promotes glioma growth.
CONCLUSIONS: RIOK1 expression is lower in glioma tissues than in non-tumor brain tissues, and is particularly lower in IDH wild-type gliomas. RIOK1 functions as a suppressor of glioma cell survival and proliferation, possibly through mTOR pathway inhibition and apoptotic pathway activation.