GPX4 inhibits apoptosis of thyroid cancer cells through regulating the FKBP8/Bcl-2 axis

Cancer Biomarkers, Journal Year: 2024, Volume and Issue: 39(4), P. 349 - 360

Published: Jan. 16, 2024

GPX4 has attracted much attention as a key molecule of cell ferroptosis, but its role in apoptosis is rarely reported, and thyroid cancer (TC) not been reported. The analysis TCGA database showed that both FKBP8 were highly expressed TC tumor tissues; expression positively correlated. immunohistochemical further confirmed tissues. In addition, the high significantly correlated with poor prognosis TC. Silencing inhibited proliferation, induced cells, reduced growth mice. co-immunoprecipitation assay revealed physical interaction between observed cells. Knockdown proliferation Rescue experiments suggested knockdown could reverse strengthens higher Bcl-2 caused by overexpression GPX4. Our results suggest GPX4/FKBP8/Bcl-2 axis promotes development inhibiting apoptosis, which provides potential molecular targets for therapeutic strategies.

Language: Английский

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Comprehensive transcriptome and scRNA‐seq analyses uncover the expression and underlying mechanism of SYNJ2 in papillary thyroid carcinoma

IET Systems Biology, Journal Year: 2024, Volume and Issue: 18(5), P. 183 - 198

Published: Oct. 1, 2024

Abstract Synaptojanin 2 (SYNJ2) has crucial role in various tumors, but its papillary thyroid carcinoma (PTC) remains unexplored. This study first detected SYNJ2 protein expression PTC using immunohistochemistry method and further assessed mRNA through chip RNA sequencing data association with clinical characteristics. Additionally, KEGG, GSVA, GSEA analyses were conducted to investigate potential biological functions, while single‐cell used explore SYNJ2's underlying mechanisms PTC. Meanwhile, immune infiltration status different groups analyzed. Besides, we investigated the checkpoint gene implemented drug sensitivity analysis. Results indicated that is highly expressed (SMD = 0.66 [95% CI: 0.17–1.15]) could distinguish between non‐PTC tissues (AUC 0.74 [0.70–0.78]). Furthermore, identified 134 intersecting genes of DEGs CEGs, mainly enriched angiogenesis epithelial‐mesenchymal transition (EMT) pathways. Subsequent analysis showed above pathways activated epithelial cells. patients high higher six common drugs. Summarily, may promote progression EMT High associated better response immunotherapy chemotherapy.

Language: Английский

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SPTBN2 regulated by miR-214-3p inhibits the proliferation and migration of colorectal cancer cells

Cellular and Molecular Biology, Journal Year: 2023, Volume and Issue: 69(14), P. 126 - 131

Published: Dec. 20, 2023

Language: Английский

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Multi-omics pan-cancer study of SPTBN2 and its value as a potential therapeutic target in pancreatic cancer

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 29, 2024

Abstract SPTBN2 is a protein-coding gene that closely related to the development of malignant tumors. However, its prognostic value and biological function in pan-cancer, especially pancreatic cancer (PAAD), have not been reported. In present study, novel exploration potential mechanism PAAD was conducted using multi-omics background pan-cancer. Via various database analysis, up-regulated expression detected most tumor tissues examined. Overexpression kidney renal clear cell patients potentially affected overall survival, disease-specific progression-free interval. PAAD, can be used as an independent factor affecting prognosis. Mutations amplification were detected, with abnormal methylation survival outcome patients. Immunoassay results demonstrate biomarker for predicting therapeutic response may influence immunotherapy efficacy by regulating levels CD8 + T cells neutrophil infiltration. Results from enrichment analysis indicated regulate via immune pathways. Thus, target based on crucial role PAAD.

Language: Английский

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Chromatin remodeling with combined FACT and BET inhibition disrupts oncogenic transcription in Diffuse Midline Glioma

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 9, 2024

Abstract Aberrant epigenetic regulation is a hallmark of Diffuse Midline Glioma (DMG), an incurable pediatric brain tumor. The H3K27M driver histone mutation leads to transcriptional dysregulation, indicating that targeting the epigenome and transcription may be key therapeutic strategies against this highly aggressive cancer. One such target Facilitates Chromatin Transcription (FACT) chaperone. We found FACT enriched at developmental gene promoters, coinciding with regions open chromatin binding motifs core DMG regulatory factors. Furthermore, interacted co-localized Bromodomain Extra-Terminal Domain (BET) protein BRD4 promoters enhancers, suggesting functional cooperation between in DMG. In vitro , combinatorial approach using inhibitor CBL0137, coupled BET inhibition revealed potent synergistic cytotoxicity across range cultures, H3K27M-mutant cells demonstrating heightened sensitivity. These results were recapitulated vivo significantly extending survival three independent orthotopic PDX models Mechanistically, we show CBL0137 treatment decreased accessibility, synergizing disrupt transcription, silencing several oncogenes including MYC, PDGFRA MDM4 as well causing alterations splicing landscape. Combined, these data highlight promise simultaneously DMG, proposing novel strategy for combating devastating

Language: Английский

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