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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
  • View Affiliations / Copyright

    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
    Copyright: © Lv et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 40
    |
    Published online on: February 6, 2025
       https://doi.org/10.3892/or.2025.8873
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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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1 

van den Bent MJ, Geurts M, French PJ, Smits M, Capper D, Bromberg JEC and Chang SM: Primary brain tumours in adults. Lancet. 402:1564–1579. 2023. View Article : Google Scholar : PubMed/NCBI

2 

Weller M, Wen PY, Chang SM, Dirven L, Lim M, Monje M and Reifenberger G: Glioma. Nat Rev Dis Primers. 10:332024. View Article : Google Scholar : PubMed/NCBI

3 

Chai X, Zhang Y, Zhang W, Feng K, Jiang Y, Zhu A, Chen X, Di L and Wang R: Tumor metabolism: A new field for the treatment of glioma. Bioconjug Chem. 35:1116–1141. 2024. View Article : Google Scholar : PubMed/NCBI

4 

Obrador E, Moreno-Murciano P, Oriol-Caballo M, López-Blanch R, Pineda B, Gutiérrez-Arroyo JL, Loras A, Gonzalez-Bonet LG, Martinez-Cadenas C, Estrela JM and Marqués-Torrejón MÁ: Glioblastoma therapy: Past, present and future. Int J Mol Sci. 25:25292024. View Article : Google Scholar : PubMed/NCBI

5 

Mishchenko TA, Turubanova VD, Gorshkova EN, Krysko O, Vedunova MV and Krysko DV: Glioma: Bridging the tumor microenvironment, patient immune profiles and novel personalized immunotherapy. Front Immunol. 14:12990642023. View Article : Google Scholar : PubMed/NCBI

6 

Weiskirchen R and Günther K: The CRP/MLP/TLP family of LIM domain proteins: Acting by connecting. BioEssays. 25:152–162. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Schallus T, Fehér K, Ulrich AS, Stier G and Muhle-Goll C: Structure and dynamics of the human muscle LIM protein. FEBS Lett. 583:1017–1022. 2009. View Article : Google Scholar : PubMed/NCBI

8 

Chang DF, Belaguli NS, Chang J and Schwartz RJ: LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac myocytes. Proc Natl Acad Sci U S A. 104:157–162. 2007. View Article : Google Scholar : PubMed/NCBI

9 

Wang J, Guan X, Zhang Y, Ge S, Zhang L, Li H, Wang X, Liu R, Ning T, Deng T, et al: Exosomal miR-27a derived from gastric cancer cells regulates the transformation of fibroblasts into cancer-associated fibroblasts. Cell Physiol Biochem. 49:869–883. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Chen CH, Ho YC, Ho HH, Chang IC, Kirsch KH, Chuang YJ, Layne MD and Yet SF: Cysteine-rich protein 2 alters p130Cas localization and inhibits vascular smooth muscle cell migration. Cardiovasc Res. 100:461–471. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Wu ML, Chen CH, Lin YT, Jheng YJ, Ho YC, Yang LT, Chen L, Layne MD and Yet SF: Divergent signaling pathways cooperatively regulate TGFbeta induction of cysteine-rich protein 2 in vascular smooth muscle cells. Cell Commun Signal. 12:222014. View Article : Google Scholar : PubMed/NCBI

12 

Hoffmann C, Mao X, Brown-Clay J, Moreau F, Al Absi A, Wurzer H, Sousa B, Schmitt F, Berchem G, Janji B and Thomas C: Hypoxia promotes breast cancer cell invasion through HIF-1alpha-mediated up-regulation of the invadopodial actin bundling protein CSRP2. Sci Rep. 8:101912018. View Article : Google Scholar : PubMed/NCBI

13 

Zhang MJ, Liu J, Wan SC, Li JX, Wang S, Fidele NB, Huang CF and Sun ZJ: CSRP2 promotes cell stemness in head and neck squamous cell carcinoma. Head Neck. 45:2161–2172. 2023. View Article : Google Scholar : PubMed/NCBI

14 

Chen L, Long X, Duan S, Liu X, Chen J, Lan J, Liu X, Huang W, Geng J and Zhou J: CSRP2 suppresses colorectal cancer progression via p130Cas/Rac1 axis-meditated ERK, PAK, and HIPPO signaling pathways. Theranostics. 10:11063–11079. 2020. View Article : Google Scholar : PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Huang J: Current developments of targeting the p53 signaling pathway for cancer treatment. Pharmacol Ther. 220:1077202021. View Article : Google Scholar : PubMed/NCBI

17 

Weiskirchen R, Moser M, Weiskirchen S, Erdel M, Dahmen S, Buettner R and Gressner AM: LIM-domain protein cysteine- and glycine-rich protein 2 (CRP2) is a novel marker of hepatic stellate cells and binding partner of the protein inhibitor of activated STAT1. Biochem J. 359:485–496. 2001. View Article : Google Scholar : PubMed/NCBI

18 

Śledzińska P, Bebyn MG, Furtak J, Kowalewski J and Lewandowska MA: Prognostic and predictive biomarkers in gliomas. Int J Mol Sci. 22:103732021. View Article : Google Scholar : PubMed/NCBI

19 

Tong X, Tang R, Xiao M, Xu J, Wang W, Zhang B, Liu J, Yu X and Shi S: Targeting cell death pathways for cancer therapy: Recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research. J Hematol Oncol. 15:1742022. View Article : Google Scholar : PubMed/NCBI

20 

Huang FY, Dai SZ, Xu WT, Xiong W, Sun Y, Huang YH, Wang JY, Lin YY, Chen H, Tan GH and Zheng WP: 3′-epi-12beta-hydroxyfroside-mediated autophagy degradation of RIPK1/RIPK3 necrosomes leads to anergy of immunogenic cell death in triple-negative breast cancer cells. Pharmacol Res. 187:1066132023. View Article : Google Scholar : PubMed/NCBI

21 

Pomlok K, Pata S, Kulaphisit M, Pangnuchar R, Wipasa J, Smith DR, Kasinrerk W and Lithanatudom P: An IgM monoclonal antibody against domain 1 of CD147 induces non-canonical RIPK-independent necroptosis in a cell type specific manner in hepatocellular carcinoma cells. Biochim Biophys Acta Mol Cell Res. 1869:1192952022. View Article : Google Scholar : PubMed/NCBI

22 

Vetrivel P, Nachimuthu S, Abuyaseer A, Bhosale PB, Ha SE, Kim HH, Park MY and Kim GS: Investigation on the cellular mechanism of prunetin evidenced through next generation sequencing and bioinformatic approaches against gastric cancer. Sci Rep. 12:118522022. View Article : Google Scholar : PubMed/NCBI

23 

Wang HL, Chang JC, Fang LW, Hsu HF, Lee LC, Yang JF, Liang MT, Hsiao PC, Wang CP, Wang SW, et al: Bulnesia sarmientoi supercritical fluid extract exhibits necroptotic effects and anti-metastatic activity on lung cancer cells. Molecules. 23:33042018. View Article : Google Scholar : PubMed/NCBI

24 

Liu B, Mink S, Wong KA, Stein N, Getman C, Dempsey PW, Wu H and Shuai K: PIAS1 selectively inhibits interferon-inducible genes and is important in innate immunity. Nat Immunol. 5:891–898. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Xue C, Yao Q, Gu X, Shi Q, Yuan X, Chu Q, Bao Z, Lu J and Li L: Evolving cognition of the JAK-STAT signaling pathway: Autoimmune disorders and cancer. Signal Transduct Target Ther. 8:2042023. View Article : Google Scholar : PubMed/NCBI

26 

Chen Y, Fang ZM, Yi X, Wei X and Jiang DS: The interaction between ferroptosis and inflammatory signaling pathways. Cell Death Dis. 14:2052023. View Article : Google Scholar : PubMed/NCBI

27 

Vier J, Groth M, Sochalska M and Kirschnek S: The anti-apoptotic Bcl-2 family protein A1/Bfl-1 regulates neutrophil survival and homeostasis and is controlled via PI3K and JAK/STAT signaling. Cell Death Dis. 7:e21032016. View Article : Google Scholar : PubMed/NCBI

28 

Yu X, Ma H, Li B, Ji Y, Du Y, Liu S, Li Z, Hao Y, Tian S, Zhao C, et al: A novel RIPK1 inhibitor reduces GVHD in mice via a nonimmunosuppressive mechanism that restores intestinal homeostasis. Blood. 141:1070–1086. 2023. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lv D, Han X, Hao L, Sun Z, Zhang A, Liu J, Liu L and Liu L: Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways. Oncol Rep 53: 40, 2025.
APA
Lv, D., Han, X., Hao, L., Sun, Z., Zhang, A., Liu, J. ... Liu, L. (2025). Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways. Oncology Reports, 53, 40. https://doi.org/10.3892/or.2025.8873
MLA
Lv, D., Han, X., Hao, L., Sun, Z., Zhang, A., Liu, J., Liu, L., Liu, L."Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways". Oncology Reports 53.3 (2025): 40.
Chicago
Lv, D., Han, X., Hao, L., Sun, Z., Zhang, A., Liu, J., Liu, L., Liu, L."Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways". Oncology Reports 53, no. 3 (2025): 40. https://doi.org/10.3892/or.2025.8873
Copy and paste a formatted citation
x
Spandidos Publications style
Lv D, Han X, Hao L, Sun Z, Zhang A, Liu J, Liu L and Liu L: Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways. Oncol Rep 53: 40, 2025.
APA
Lv, D., Han, X., Hao, L., Sun, Z., Zhang, A., Liu, J. ... Liu, L. (2025). Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways. Oncology Reports, 53, 40. https://doi.org/10.3892/or.2025.8873
MLA
Lv, D., Han, X., Hao, L., Sun, Z., Zhang, A., Liu, J., Liu, L., Liu, L."Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways". Oncology Reports 53.3 (2025): 40.
Chicago
Lv, D., Han, X., Hao, L., Sun, Z., Zhang, A., Liu, J., Liu, L., Liu, L."Cysteine‑ and glycine‑rich protein 2: A vital regulator that inhibits necroptosis glioma cell by activating the JAK‑STAT1 pathways". Oncology Reports 53, no. 3 (2025): 40. https://doi.org/10.3892/or.2025.8873
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