NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination DOI Creative Commons
Zhen Chen, Weilong Wang,

Jinghan Hou

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Ноя. 18, 2024

Abstract The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated function is tightly controlled posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of ubiquitin ligases human cancers. Here, we reported that NEDD4L, E3 ligases, inhibited esophageal squamous cell carcinoma (ESCC) facilitated ferroptosis ubiquitination xCT. NEDD4L expression was declined ESCC associated with invasion, lymph node metastasis distant metastasis. Silencing triggered growth. Meanwhile, knock down prevented the accumulation ROS, elevated level GSH, reduced content MDA cells, thereby inhibiting Mechanistically, directly bound to ∆CT domain through its WW HECT domain. More importantly, promoted degradation facilitating polyubiquitination cells. Collectively, these findings suggest crucial governing stability mediating ESCC.

Язык: Английский

Arginine methylation and respiratory disease DOI
Binbin Zhang, Youhong Guan,

Daxiong Zeng

и другие.

Translational research, Год журнала: 2024, Номер 272, С. 140 - 150

Опубликована: Март 5, 2024

Язык: Английский

Процитировано

1
Gelsolin knockdown confers radiosensitivity to glioblastoma cells DOI Creative Commons

Dezhi Gao,

Tao Jiang, Yanwei Liu

и другие.

Cancer Medicine, Год журнала: 2024, Номер 13(10)

Опубликована: Май 1, 2024

Abstract Objective Radiotherapy (RT) is a cornerstone of the glioblastoma (GBM) treatment. However, resistance tumour cells to radiation results in early recurrence. The mechanisms underlying GBM radioresistance remain unclear. Screening for differentially expressed genes (DEGs) related might be potential solution this problem. Method RT‐associated DEGs were screened based on RNA sequencing 15 paired primary and recurrent GBMs. mRNA protein expression candidate validated Chinese Genome Atlas (CGGA) dataset 18 cases samples. relationship between gene was confirmed irradiated cells. association with clinical characteristics survival investigated CGGA TCGA dataset. Biological function pathway analysis explored by ontology analysis. radiosensitivity verified using cell counting Kit‐8, comet, colony formation assays vitro subcutaneous xenograft experiments vivo. Results Gelsolin (GSN) selected further study. GSN significant elevated up‐regulated lines. High enriched malignant phenotype glioma. Moreover, high associated poor prognosis. Further investigation demonstrated that GSN‐knockdown (GSN‐KD) combined RT significantly inhibited proliferation enhanced vivo vitro. Mechanistically, GSN‐KD could lead more serious DNA damage promotes apoptosis after RT. Conclusion Radiation induced GSN. enhance GBM.

Язык: Английский

Процитировано

1
Stanniocalcin-2 expression in glioblastoma – A novel prognostic biomarker: An observational study DOI Creative Commons
Asım Armağan Aydın, Şenay Yıldırım

Medicine, Год журнала: 2024, Номер 103(28), С. e38913 - e38913

Опубликована: Июль 12, 2024

The objective of this study was to assess the prognostic relevance Stanniocalcin-2 (STC2) expression, as determined via immunohistochemistry in tumor tissue, a cohort 83 patients diagnosed with glioblastoma who underwent maximal safe surgical resection followed by radiotherapy concurrent adjuvant temozolomide. STC2 expression levels were categorized using 3-tiered semiquantitative system: negative (level 0−), low 1+), and high (levels 2 + 3+). Patients into distinct groups according their levels: (−/+) positive (++/+++). primary outcome measure relationship between progression-free survival (PFS), overall (OS) serving secondary endpoint. Kaplan–Meier analysis confirmed that exhibiting had significantly shorter OS (8 vs 20 months, P < .001) PFS (6 18 than those or expression. Multivariate revealed an independent factor for both (hazard ratio: 0.4; 95% confidence interval: 0.2–0.8; .05) 0.3; 0.2–0.4; glioblastoma. Furthermore, elevated GBM correlated several established aggressive clinicopathological characteristics, including advanced age (≥65 years), ECOG PS (≥2), isocitrate dehydrogenase mutation negativity. These findings underscore heightened within tissue functions adverse marker, correlating risk progression reduced OS. Therapeutic interventions targeting AKT-mTOR, ERK1-2, mitogen-activated protein kinase pathways well immune checkpoint inhibitors vascular endothelial growth blockade, potential forthcoming antibody–drug conjugates molecule, have broaden scope combined treatment strategies.

Язык: Английский

Процитировано

1
Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress DOI Creative Commons
Shuo Qie, Hailin Xiong, Yaqi Liu

и другие.

Cell Death and Disease, Год журнала: 2024, Номер 15(8)

Опубликована: Авг. 6, 2024

Abstract Solid tumours often endure nutrient insufficiency during progression. How tumour cells adapt to temporal and spatial remains unclear. We previously identified STC2 as one of the most upregulated genes in exposed by transcriptome screening, indicating potential cellular adaptation insufficiency. However, molecular mechanisms underlying induction subsequent remain elusive. Here, we report that protein is dramatically increased secreted into culture media Gln-/Glc- deprivation. promoter contains cis -elements are activated ATF4 p65/RelA, two transcription factors a variety stress. Biologically, secretion promote cell survival but attenuate proliferation insufficiency, thus switching priority cancer from survival. Loss impairs growth inducing both apoptosis necrosis mouse xenografts. Mechanistically, under insufficient conditions, have levels reactive oxygen species (ROS), lack further elevates ROS lead apoptosis. RNA-Seq analyses reveal suppresses expression monoamine oxidase B (MAOB), mitochondrial membrane enzyme produces ROS. Moreover, negative correlation between MAOB also human samples. Importantly, administration recombinant effectively well apoptosis, suggesting functions an autocrine/paracrine manner. Taken together, our findings indicate induces expression, which turn governs through maintenance redox homoeostasis, highlighting therapeutic target for treatment.

Язык: Английский

Процитировано

1
NEDD4L contributes to ferroptosis and cell growth inhibition in esophageal squamous cell carcinoma by facilitating xCT ubiquitination DOI Creative Commons
Zhen Chen, Weilong Wang,

Jinghan Hou

и другие.

Cell Death Discovery, Год журнала: 2024, Номер 10(1)

Опубликована: Ноя. 18, 2024

Abstract The oncogene xCT plays an indispensable role in tumor growth by protecting cancer cells from oxidative stress and ferroptosis. Emerging evidence indicated function is tightly controlled posttranslational modifications, especially ubiquitination. However, it still remains unclear what specific regulatory mechanism of ubiquitin ligases human cancers. Here, we reported that NEDD4L, E3 ligases, inhibited esophageal squamous cell carcinoma (ESCC) facilitated ferroptosis ubiquitination xCT. NEDD4L expression was declined ESCC associated with invasion, lymph node metastasis distant metastasis. Silencing triggered growth. Meanwhile, knock down prevented the accumulation ROS, elevated level GSH, reduced content MDA cells, thereby inhibiting Mechanistically, directly bound to ∆CT domain through its WW HECT domain. More importantly, promoted degradation facilitating polyubiquitination cells. Collectively, these findings suggest crucial governing stability mediating ESCC.

Язык: Английский

Процитировано

1