Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways

Lv,Dongsheng; Han,Xu; Hao,Liang; Sun,Zhimin; Zhang,Aobo; Liu,Jing; Liu,Liang; Liu,Liqiang

doi:10.3892/or.2025.8873

Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways

Authors:
- Dongsheng Lv
- Xu Han
- Liang Hao
- Zhimin Sun
- Aobo Zhang
- Jing Liu
- Liang Liu
- Liqiang Liu
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Affiliations: Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China, Department of Neurology, The Second Hospital of Shijiazhuang, Shijiazhuang, Hebei 050051, P.R. China, Department of Neurosurgery, The Third Hospital of Shijiazhuang, Shijiazhuang, Hebei 050011, P.R. China, Department of Neurosurgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Institute of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: February 6, 2025 https://doi.org/10.3892/or.2025.8873
Article Number: 40
Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cysteine‑ and glycine‑rich protein 2 (CSRP2) are closely associated with tumor invasion and metastasis. CSRP2 is significantly upregulated in glioma tissues and is associated with the clinical stage of the tumor. Overexpression of CSRP2 in glioma cells promotes the proliferation and metastasis of cancer cells, whereas CSRP2 knockdown inhibits the biological functions of tumor cells. Transcriptome sequencing of CSRP2‑knockdown U251M cells revealed that silencing of CSRP2 inhibited the JAK‑STAT1 signaling pathway, and differentially expressed genes were significantly enriched in cell processes related to necroptosis. Experiments on necroptosis in glioma cells using flow cytometry, Hoechst 33342/PI dual staining and transmission electron microscopy indicated that CSRP2 overexpression inhibited necroptosis in glioma cells. Western blotting results showed that overexpression of CSRP2 activated the JAK‑STAT1 signaling pathway, while the addition of the pathway inhibitor ruxolitinib promoted the phosphorylation of necroptosis proteins RIPK1, RIPK3 and MLKL. Therefore, it was hypothesized that CSRP2 maintains JAK‑STAT1 activation by inhibiting the protein inhibitor of activated STAT1, which then inhibits the necrotizing apoptosis of glioma cells.

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