BAG2 inhibits the proliferation and migration of cervical cancer by slowing the degradation of STING
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ABSTRACT:
PROVIDER: PRJNA1175601 | ENA |
REPOSITORIES: ENA
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Project description:The fourth most prevalent illness in the world among women, cervical cancer has significant negative effects on both health and the economy in addition to high rates of morbidity and death. Understanding its molecular basis to guide clinical management is critical. STING, an innate immune sensor that induces type I interferon, plays a key role in enhancing anti-tumor activity. Despite the growing interest in the role played by STING in cervical cancer, the homeostatic regulatory mechanisms of STING in cervical cancer remain unknown. Here, we found that the BAG2-STUB1 complex regulates ubiquitin proteasomal degradation of STING, which affects the development of cervical cancer. Mechanistically, BAG2 inhibits ubiquitination of STING and stabilizes it by interacting with STING. Specifically, BAG2 inhibits STUB1 from linking the K48-conjugated ubiquitin chains at K338 and K370 of STING by forming a complex with STUB1. Functionally, upregulation of BAG2 expression could inhibit cervical cancer progression by activating the type I interferon response in a STING-dependent manner. Importantly, clinical cervical cancer samples showed a positive correlation between BAG2 and STING expression, and low BAG2 expression was strongly associated with clinical progression and poor prognosis in cervical cancer. Together, these findings describe the molecular mechanism by which the BAG2-STUB1 complex mediates the homeostatic regulation of STING, highlighting the important potential role of BAG2 in the diagnosis and treatment of cervical cancer.
2025-08-27 | GSE279947 | GEO
Project description:Methylation modifications play pertinent roles in regulating gene expression and various biological processes. The silencing of the demethylated modifier TET1 can affect the expressions of key oncogenes or tumor suppressor genes, thus contributing to tumor formation. Nonetheless, how TET1 affects the progression of cervical cancer is yet to be elucidated. In this study, we found that the expression of TET1 was significantly downregulated in cervical cancer tissues. Functionally, TET1 knockdown in cervical cancer cells can promote cell proliferation, migration, invasion, cervical xenograft tumor formation and EMT. On the contrary, its overexpression can reverse the aforementioned processes. Moreover, the autophagy level of cervical cancer cells can be enhanced after TET1 knockdown. Mechanistically, methylated DNA immunoprecipitation (MeDIP)-sequencing and MeDIP quantitative real-time PCR revealed that TET1 mediates the methylation of autophagy promoter regions. These findings suggest that TET1 affects the malignant biological behavior of cervical cancer cells by altering the methylation levels of autophagy genes NKRF and HIST1H2AK, but the specific mechanism needs to be investigated further.
2024-03-13 | GSE236315 | GEO
Project description:Methylation modifications play pertinent roles in regulating gene expression and various biological processes. The silencing of the demethylated modifier TET1 can affect the expressions of key oncogenes or tumor suppressor genes, thus contributing to tumor formation. Nonetheless, how TET1 affects the progression of cervical cancer is yet to be elucidated. In this study, we found that the expression of TET1 was significantly downregulated in cervical cancer tissues. Functionally, TET1 knockdown in cervical cancer cells can promote cell proliferation, migration, invasion, cervical xenograft tumor formation and EMT. On the contrary, its overexpression can reverse the aforementioned processes. Moreover, the autophagy level of cervical cancer cells can be enhanced after TET1 knockdown. Mechanistically, methylated DNA immunoprecipitation (MeDIP)-sequencing and MeDIP quantitative real-time PCR revealed that TET1 mediates the methylation of autophagy promoter regions. These findings suggest that TET1 affects the malignant biological behavior of cervical cancer cells by altering the methylation levels of autophagy genes NKRF and HIST1H2AK, but the specific mechanism needs to be investigated further.
2024-03-13 | GSE236396 | GEO
Project description:TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy
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Project description:The present study aimed to explore the role of macrophage migration inhibitory factors in cervical squamous cell carcinoma (CSCC) recurrence and metastasis.
2025-01-24 | GSE280733 | GEO
Project description:STING, the pivotal adaptor protein of CGAS-STING signaling, is critical for type I IFN production of innate immunity. However, excessive or prolonged activation of STING is associated with autoinflammatory and autoimmune diseases. Thus, preventing STING from over-activation is important to maintain immune homeostasis. Here, we reported that SESN1 was essential to prevent the excessive activation of STING-mediated type I IFN signaling through autophagic degradation of STING.
2025-05-29 | GSE266409 | GEO
Project description:Despite the demonstrated efficacy of immune checkpoint blockade therapies in various tumors, their efficacy in cervical cancer is limited by factors such as the need for positive PD-L1 expression and the development of drug resistance. A crucial pro-inflammatory cytokine, macrophage migration inhibitory factor (MIF), is highly expressed in various cancers and contributes to tumor progression by regulating inflammatory responses and the tumor microenvironment. The present study aimed to explore the role of macrophage migration inhibitory factors in cervical squamous cell carcinoma (CSCC) recurrence and metastasis. Western blotting, reverse transcription quantitative PCR, cell-counting kit 8 assay, flow cytometry, and ELISA were used to investigate the effects of MIF on CSCC progression and formation of inflammasomes. Transcriptome and proteome sequencing were combined to screen for key effector proteins of MIF. Moreover, in vitro co-culture experiments, Transwell assays, and flow cytometry were used to evaluate the roles of MIF and TSC22 domain family protein 3 (TSC22D3) as inflammatory tumor-promoting factors in macrophage recruitment and polarization induction. The results indicated that MIF was highly expressed in CSCC with lymph node metastasis, positively correlated with cervical cancer stage, and associated with poor prognosis. MIF was found to promote CSCC progression and linked to inflammasome activation. Multi-omics screening results indicated that TSC22D3 may be a crucial interacting gene of MIC. Moreover, MIF and TSC22D3 could facilitate inflammasome activation, macrophage recruitment, and M2 polarization. Therefore, MIF and TSC22D3 can induce macrophage infiltration in cervical cancer lesions and affect the tumor microenvironment by polarizing macrophages toward the M2 phenotype, promoting CSCC progression. This study highlights the potential of targeting the MIF-TSC22D3 axis as a novel therapeutic strategy and offering a promising avenue for improving the efficacy of immunotherapy in treatin
2025-01-26 | PXD057462 | Pride
Project description:The potential risk of P2Y12 antagonists for cancer treatment is controversial. Here we show that PSB 0739, a P2Y12 antagonist inhibits human cervical cancer cells (Hela and SiHa) migration without modifying cell proliferation. We identify that the co-acetylation and lactylation of epithelial-mesenchymal transition (EMT)-related protein NCL, MYH9, CTTN, S100A6, and ALDOA revealed by proteomic analysis of posttranslational modifications (PTM), are responsible for the PSB0739-induced migration inhibition in human cervical cancer cells. Our data suggest that as one of P2Y12 antagonists, PSB 0739 has no risk in cervical cancer cell migration. The co-modification of acetylation and lactylation of EMT-associated proteins would be novel promising targets to develop new drug for cancer cell migration beyond contributing the potential mechanism of the use of PSB0379 in human cervical cancer cells.
2023-04-06 | PXD041371 |
Project description:TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy [MeDIP-Seq]
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Project description:TET1 inhibits the migration and invasion of cervical cancer cells by regulating autophagy [RNA-seq]
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