Archivos espanoles de urologia · 2025
OTUB1 Promotes Stem-like Properties in Bladder Cancer by Stabilising SLC7A11 and Suppressing Ferroptosis through Deubiquitination.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhong Xintai, Xiao Meiling, Su Feng, Shi Jingbin, Huang Tao
Аннотация
BACKGROUND: Cancer stem cells (CSCs) contribute to bladder cancer (BCa) progression and treatment resistance. Ferroptosis, an iron-dependent cell death, influences CSC maintenance, but its post-translational regulation remains unclear. This study investigated how the deubiquitinase OTUB1 regulated ferroptosis and CSC-like traits in BCa through interaction with SLC7A11.
METHODS: OTUB1 expression was assessed in clinical BCa tissue pairs (tumour vs adjacent normal) collected from patients undergoing surgical resection and in cell lines. Gain- and loss-of-function models were established in BCa cells. Cell viability, stemness capacity and ferroptosis markers were evaluated using Cell Counting Kit-8 (CCK-8) assay, Western blot, sphere formation assay, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, reactive oxygen species (ROS) detection, enzyme-linked immunosorbent assay (ELISA) and co-immunoprecipitation.
RESULTS: OTUB1 was significantly upregulated in BCa cells and tissues relative to normal controls (p < 0.01). OTUB1 overexpression significantly enhanced BCa cell viability, self-renewal capacity and stemness marker expression but reduced ferroptosisassociated indicators (ROS, malondialdehyde (MDA) and ferrous iron (Fe2+)) (p < 0.01). Conversely, OTUB1 knockdown impaired stem-like traits (p < 0.01) and triggered ferroptosis (p < 0.01). Mechanistically, OTUB1 directly interacted with SLC7A11, decreased its ubiquitination and stabilised its protein expression (p < 0.01). Notably, ectopic SLC7A11 expression rescued the impaired stemness and ferroptosis induction caused by OTUB1 knockdown (p < 0.01).
CONCLUSIONS: OTUB1 inhibits ferroptosis and sustains CSC-like features in BCa by deubiquitinating and stabilising SLC7A11. The OTUB1-SLC7A11 axis represents a novel regulatory mechanism of CSC maintenance and may serve as an intervention point in BCa.
METHODS: OTUB1 expression was assessed in clinical BCa tissue pairs (tumour vs adjacent normal) collected from patients undergoing surgical resection and in cell lines. Gain- and loss-of-function models were established in BCa cells. Cell viability, stemness capacity and ferroptosis markers were evaluated using Cell Counting Kit-8 (CCK-8) assay, Western blot, sphere formation assay, quantitative real-time polymerase chain reaction (qRT-PCR), immunofluorescence, reactive oxygen species (ROS) detection, enzyme-linked immunosorbent assay (ELISA) and co-immunoprecipitation.
RESULTS: OTUB1 was significantly upregulated in BCa cells and tissues relative to normal controls (p < 0.01). OTUB1 overexpression significantly enhanced BCa cell viability, self-renewal capacity and stemness marker expression but reduced ferroptosisassociated indicators (ROS, malondialdehyde (MDA) and ferrous iron (Fe2+)) (p < 0.01). Conversely, OTUB1 knockdown impaired stem-like traits (p < 0.01) and triggered ferroptosis (p < 0.01). Mechanistically, OTUB1 directly interacted with SLC7A11, decreased its ubiquitination and stabilised its protein expression (p < 0.01). Notably, ectopic SLC7A11 expression rescued the impaired stemness and ferroptosis induction caused by OTUB1 knockdown (p < 0.01).
CONCLUSIONS: OTUB1 inhibits ferroptosis and sustains CSC-like features in BCa by deubiquitinating and stabilising SLC7A11. The OTUB1-SLC7A11 axis represents a novel regulatory mechanism of CSC maintenance and may serve as an intervention point in BCa.