DDX21 Controls Cell Cycle Progression and Autophagy in Pancreatic Cancer Cells DOI Open Access

Adriana Leccese,

Veronica Ruta, Valentina Panzeri

и другие.

Cancers, Год журнала: 2025, Номер 17(4), С. 570 - 570

Опубликована: Фев. 7, 2025

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer. Late diagnosis and acquisition of chemoresistance contribute to its dismal prognosis. While surgical resection improved the clinical outcome patients, only ~20% them are eligible due advanced disease at diagnosis. Thus, development new therapeutic approaches master priority for an management this The helicase DDX21 was proposed as prognostic marker in several tumors, including PDAC. Methods:DDX21 expression evaluated PDAC samples cell lines; RNA sequencing bioinformatics analyses DDX21-depleted PANC-1 silenced cells; functional autophagy, cycle proliferation. Results: expressed higher levels liver metastasis patients. Transcriptomics cells revealed enrichment genes involved autophagy progression. inactivation by interference enhanced basal autophagic flux altered reducing rate G1-S transition. Coherently, proliferation clonogenic activity significantly reduced. Conclusions: Our results support oncogenic role uncover regulation autophagy.

Язык: Английский

PRMT1-Catalyzed NUSAP1 Methylation Enhances Notch2 Signaling and 5-FU Resistance in Gastric Cancer DOI Creative Commons

Feng Wang,

Steve Jiang,

Guoli Li

и другие.

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Фев. 3, 2025

Abstract 5-Fluorouracil (5-FU) resistance remains a significant challenge in the treatment of gastric cancer, limiting its clinical efficacy. Our study identifies NUSAP1, nucleolar and spindle-associated protein, as key driver 5-FU cancer. Proteomic analyses 5-FU-resistant cancer cell lines revealed that NUSAP1 is significantly upregulated, functional studies demonstrated essential role promoting resistance, proliferation, migration, invasion, tumor growth. Mechanistic investigations undergoes asymmetric dimethylation (ADMA) at R418 R422, mediated by PRMT1, with R422 site being critical for function. interacts PEST domain Notch2 through site, inhibiting ubiquitination stabilizing expression, thereby activating signaling pathway. This pathway closely linked to progression chemoresistance. Inhibition PRMT1 or mutation abrogated NUSAP1’s ability stabilize regulate downstream signaling. These findings unveil novel mechanism which promotes highlight therapeutic potential targeting NUSAP1-Notch2 axis overcoming

Язык: Английский

Процитировано

0
DDX21 Controls Cell Cycle Progression and Autophagy in Pancreatic Cancer Cells DOI Open Access

Adriana Leccese,

Veronica Ruta, Valentina Panzeri

и другие.

Cancers, Год журнала: 2025, Номер 17(4), С. 570 - 570

Опубликована: Фев. 7, 2025

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer. Late diagnosis and acquisition of chemoresistance contribute to its dismal prognosis. While surgical resection improved the clinical outcome patients, only ~20% them are eligible due advanced disease at diagnosis. Thus, development new therapeutic approaches master priority for an management this The helicase DDX21 was proposed as prognostic marker in several tumors, including PDAC. Methods:DDX21 expression evaluated PDAC samples cell lines; RNA sequencing bioinformatics analyses DDX21-depleted PANC-1 silenced cells; functional autophagy, cycle proliferation. Results: expressed higher levels liver metastasis patients. Transcriptomics cells revealed enrichment genes involved autophagy progression. inactivation by interference enhanced basal autophagic flux altered reducing rate G1-S transition. Coherently, proliferation clonogenic activity significantly reduced. Conclusions: Our results support oncogenic role uncover regulation autophagy.

Язык: Английский

Процитировано

0