Life sciences · 2024
Transcription factor PRRX1-activated ANXA6 facilitates EGFR-PKCα complex formation and enhances cisplatin sensitivity in bladder cancer.
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.
Cao Jinlong, Chen Siyu, Wang Jirong, Fan Xinpeng, Liu Shanhui, Li Xiaoran, Yang Li
Аннотация
BACKGROUND: Tumor resistance to cisplatin represents a major clinical challenge, particularly in bladder cancer (BC). ANXA6 is a member of annexin family, and its role in cisplatin resistance remains unclear. This study explores ANXA6's role in promoting cisplatin sensitivity.
METHODS: Bioinformatics analyses and clinical specimen verifications assessed the correlation between ANXA6 and cisplatin treatment. A series of assays, including CCK-8, clone formation assay, flow cytometry assays for reactive oxygen species (ROS) and apoptosis, and comet assays, were used to confirm ANXA6's role in enhancing cisplatin sensitivity and re-sensitizing resistant BC cells. Mass spectrometry, immunofluorescence, and co-immunoprecipitation experiments elucidated ANXA6's role in enhancing PKCα/EGFR complex formation and inhibiting the EGFR pathway. ChIP-PCR and dual-luciferase assays determined PRRX1's regulatory role on ANXA6 transcription. Finally, the impact of ANXA6 in vivo was evaluated using xenograft models.
RESULTS: Bioinformatics analyses showed a significant correlation between ANXA6 expression and cisplatin sensitivity. In vitro and in vivo experiments confirmed that ANXA6 was a new target for cisplatin treatment. ANXA6 overexpression not only enhanced cell viability inhibition, DNA damage and apoptosis caused by cisplatin, but also re-sensitized cisplatin-resistant cells. Mechanistically, ANXA6 promotes PKCα/EGFR complex formation, inhibiting EGFR phosphorylation and downstream AKT and ERK1/2. Moreover, PRRX1 was identified as a transcription factor promoting ANXA6 expression, thereby augmenting the cytotoxic effects of cisplatin.
CONCLUSION: Our study reveals the mechanism by which ANXA6 enhances cisplatin sensitivity and re-sensitizes resistant cells. The roles of PRRX1 and ANXA6 in cisplatin resistance offer new therapeutic targets to overcome cisplatin resistance in clinical practice.
METHODS: Bioinformatics analyses and clinical specimen verifications assessed the correlation between ANXA6 and cisplatin treatment. A series of assays, including CCK-8, clone formation assay, flow cytometry assays for reactive oxygen species (ROS) and apoptosis, and comet assays, were used to confirm ANXA6's role in enhancing cisplatin sensitivity and re-sensitizing resistant BC cells. Mass spectrometry, immunofluorescence, and co-immunoprecipitation experiments elucidated ANXA6's role in enhancing PKCα/EGFR complex formation and inhibiting the EGFR pathway. ChIP-PCR and dual-luciferase assays determined PRRX1's regulatory role on ANXA6 transcription. Finally, the impact of ANXA6 in vivo was evaluated using xenograft models.
RESULTS: Bioinformatics analyses showed a significant correlation between ANXA6 expression and cisplatin sensitivity. In vitro and in vivo experiments confirmed that ANXA6 was a new target for cisplatin treatment. ANXA6 overexpression not only enhanced cell viability inhibition, DNA damage and apoptosis caused by cisplatin, but also re-sensitized cisplatin-resistant cells. Mechanistically, ANXA6 promotes PKCα/EGFR complex formation, inhibiting EGFR phosphorylation and downstream AKT and ERK1/2. Moreover, PRRX1 was identified as a transcription factor promoting ANXA6 expression, thereby augmenting the cytotoxic effects of cisplatin.
CONCLUSION: Our study reveals the mechanism by which ANXA6 enhances cisplatin sensitivity and re-sensitizes resistant cells. The roles of PRRX1 and ANXA6 in cisplatin resistance offer new therapeutic targets to overcome cisplatin resistance in clinical practice.