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CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression.

作者信息

Rong Zeyin, Xu Jin, Yang Jianhui, Wang Wei, Tang Rong, Zhang Zifeng, Tan Zhen, Meng Qingcai, Hua Jie, Liu Jiang, Zhang Bo, Liang Chen, Yu Xianjun, Shi Si

机构信息

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Cancer Res. 2024 Dec 16;84(24):4246-4263. doi: 10.1158/0008-5472.CAN-23-3596.


DOI:10.1158/0008-5472.CAN-23-3596
PMID:39288082
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor with limited treatment options and poor patient survival. Circular RNAs (circRNA) play crucial regulatory roles in the occurrence and development of various cancers, including PDAC. In this study, using circRNA sequencing of diverse PDAC samples, we identified circRREB1 as an oncogenic circRNA that is significantly upregulated in PDAC and is correlated with an unfavorable patient prognosis. Functionally, loss of circRREB1 markedly inhibited glycolysis and stemness, whereas elevated circRREB1 elicited the opposite effects. Mechanistically, circRREB1 interacted with PGK1, disrupting the association between PTEN and PGK1 and increasing PGK1 phosphorylation to activate glycolytic flux. Moreover, circRREB1 promoted WNT7B transcription by directly interacting with YBX1 and facilitating its nuclear translocation, consequently activating the Wnt/β-catenin signaling pathway to maintain PDAC stemness. Overall, these results highlight circRREB1 as a key regulator of metabolic and stemness properties of PDAC. Significance: CircRREB1 stimulates PGK1 to induce glycolysis and activates the Wnt/β-catenin signaling pathway to maintain stemness in pancreatic cancer, indicating the potential of circRREB1 as a biomarker and therapeutic target.

摘要

相似文献

[1]
CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression.

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[2]
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[3]
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[10]
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引用本文的文献

[1]
EPS8L2 drives colorectal cancer cell proliferation and migration via YBX1-dependent activation of G3BP2 transcription.

Cell Death Dis. 2025-8-10

[2]
Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.

Signal Transduct Target Ther. 2025-7-18

[3]
ACSF2-PGK1 interaction promotes ferroptosis in renal tubular epithelial cells of diabetic nephropathy by regulating Keap1/Nrf2 signaling.

Redox Rep. 2025-12

[4]
tRF-1:28-Val-CAC-2 promotes the development of nasopharyngeal cancer by targeting EPHB2.

Front Oncol. 2025-5-23

[5]
Role of noncoding RNA and protein interaction in pancreatic cancer.

Chin Med J (Engl). 2025-5-5

[6]
Circular RNA in Pancreatic Cancer: Biogenesis, Mechanism, Function and Clinical Application.

Int J Med Sci. 2025-2-28

[7]
Circular RNAs in cancer.

MedComm (2020). 2025-2-2

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