HSPA5-mediated glioma hypoxia tolerance promotes M2 macrophage polarization under hypoxic microenvironment DOI Creative Commons
Yang He, Yanpeng Xue,

Qing Jiang

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 147, С. 113856 - 113856

Опубликована: Дек. 30, 2024

The tumor microenvironment (TME), with hallmark features of hypoxia and immunosuppression, plays a crucial role in the progression various solid tumors. However, intricate interplay between formation immune glioma remains incompletely understood. In present study, we initially identified genes associated through GSEA IMMPORT database analysis. We subsequently hypoxia- immune-related prognosis further cross-analysis multidatabase integrated HSPA5 was ultimately as potential target gene related to hypoxic glioma. Furthermore, conducted MTT, colony formation, EdU, migration invasion assays intracranial orthotopic model analysis evaluate impact interfering expression on microenvironments found that is highly expressed cells tissues poor prognosis. Further investigation revealed promotes malignant biological characteristics reshaping Immunosuppressive phenotype tumor-associated macrophages (TAMs) upregulation HIF-1α/HSPA5 axis. Silencing alleviated tolerance induced polarization TAMs toward M1 phenotype. could exhibit tumor-suppressive effect. These observations suggest by inducing TAMs. Therefore, targeting may be novel therapeutic strategy for

Язык: Английский

FTO/miR-503-5p/USP10 axis regulates neuronal endoplasmic reticulum stress-mediated apoptosis in ischemic stroke DOI
Qiang Peng, Shiyao Wang,

Shi Huang

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 149, С. 114150 - 114150

Опубликована: Фев. 3, 2025

Язык: Английский

Процитировано

0
Deubiquitinases as novel therapeutic targets in colorectal cancer DOI Open Access

Noor Al Shukri,

Razik Bin Abdul Momin

Asia-Pacific Journal of Oncology, Год журнала: 2025, Номер unknown

Опубликована: Март 17, 2025

Colorectal cancer (CRC) is one of the leading causes cancer-related mortality and third most prevalent malignant tumor in world. In recent years, key role protein post-translational modifications, especially ubiquitination deubiquitination tumorigenesis progression has gradually been revealed. Deuubiquitinating Enzymes (DUBs) play an important CRC cell proliferation, apoptosis, autophagy, immune escape, chemotherapy resistance by removing ubiquitin chains from proteins, regulating stability, activity, subcellular localization. Research shown that DUBs such as USP7, USP10, USP22 promote metastasis stabilizing associated proteins β-catenin, p53, c-Myc, activating signaling pathways Wnt/β-catenin ERK/MAPK. addition, exacerbate malignancy microenvironment (TME) inflammatory responses, polarization macrophages. Meanwhile, are closely related to resistance, decreased drug sensitivity maintaining stability targets or enhancing anti-apoptotic function. At present, small molecule inhibitors targeting have made certain progress, USP7 inhibitor P5091 USP14 IU1, providing new directions for treatment CRC. However, clinical applications still face challenges selectivity safety concerns. summary, in-depth research on molecular mechanisms CRC, development more efficient specific targeted inhibitors, exploration their combined application with other therapeutic methods expected provide strategies diagnosis

Язык: Английский

Процитировано

0
RNF128 promotes gastric cancer progression by inhibiting autophagy-dependent ferroptosis through Beclin1 ubiquitination DOI Creative Commons

Zhenguo Zhu,

Qishuai Chen,

Siyi Song

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Апрель 19, 2025

Abstract As an important protein post-translational modification process, ubiquitination plays indispensable role in the regulation of gastric cancer (GC) occurrence and development. And recent studies have demonstrated that this is closely related to regulated cell death. This suggests our therapeutic approach inhibit malignant progression GC by regulating intracellular death mode through becomes possible. Although has been well described some tumorigenesis, its potential specific mechanisms are still unknown. In present study, we identified RNF128, E3 ubiquitin ligase with a RING structural domain, whose expression was significantly increased GC. In-depth showed knockdown RNF128 inhibited proliferation autophagic flux lipid peroxidation production, hypothesized autophagy-dependent ferroptosis might be main mediated RNF128. Mechanistically, directly binds ubiquitinates degradation Beclin1 PA domain inhibits Beclin1/solute transport family 7 member 11(SLC7A11)/glutathione peroxidase 4(GPX4) axis. Taken together, study reports for first time acts as tumor promoter GCs targeting Beclin1. These data provide new insights into activation expected strategy molecular therapy clinical patients.

Язык: Английский

Процитировано

0
HSPA5-mediated glioma hypoxia tolerance promotes M2 macrophage polarization under hypoxic microenvironment DOI Creative Commons
Yang He, Yanpeng Xue,

Qing Jiang

и другие.

International Immunopharmacology, Год журнала: 2024, Номер 147, С. 113856 - 113856

Опубликована: Дек. 30, 2024

The tumor microenvironment (TME), with hallmark features of hypoxia and immunosuppression, plays a crucial role in the progression various solid tumors. However, intricate interplay between formation immune glioma remains incompletely understood. In present study, we initially identified genes associated through GSEA IMMPORT database analysis. We subsequently hypoxia- immune-related prognosis further cross-analysis multidatabase integrated HSPA5 was ultimately as potential target gene related to hypoxic glioma. Furthermore, conducted MTT, colony formation, EdU, migration invasion assays intracranial orthotopic model analysis evaluate impact interfering expression on microenvironments found that is highly expressed cells tissues poor prognosis. Further investigation revealed promotes malignant biological characteristics reshaping Immunosuppressive phenotype tumor-associated macrophages (TAMs) upregulation HIF-1α/HSPA5 axis. Silencing alleviated tolerance induced polarization TAMs toward M1 phenotype. could exhibit tumor-suppressive effect. These observations suggest by inducing TAMs. Therefore, targeting may be novel therapeutic strategy for

Язык: Английский

Процитировано

1