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Updated: May 11, 2026

Efficient Differentiation of Pluripotent Stem Cells to NKX6-1+ Pancreatic Progenitors
Published on: March 7, 2017
ONECUT3 activates the TRIM46-NF-κB pathway to promote the development of pancreatic cancer
Linyi Xu1, Xinqiang Wan2, Xiangxiang Shan3
1The Yancheng Clinical College of Xuzhou Medical University, 224001, China.
Abstract:
Pancreatic cancer (PC) remains one of the deadliest cancers, characterized by its high aggressiveness and low overall survival, with chemotherapy and immunotherapy showing limited efficacy. It is essential to investigate the molecular mechanisms driving the PC progression. In this study, we showed that One Cut homeobox 3 (ONECUT3) acted as an oncogene promoting PC progression and observed a significant increase of ONECUT3 levels in PC tissues and cells. The reduced ONECUT3 expression was positively correlated with decreased tumor volumes and weight, and the depressed proliferation, migration and invasion abilities. Mechanistically, ONECUT3 directly bound to the promoter of tripartite motif-containing 46 (TRIM46) and transcriptionally upregulated its expression. Tripartite motif (TRIM)-containing proteins have been identified as closely linked to the advancement of tumors. However, the role of TRIM46 in PC remains largely unexplored. The expression of ONECUT3 was found to be positively linked with TRIM46 in human PC tissues. The upregulation of TRIM46 rescued ONECUT3 knockdown-induced suppression of cell proliferation, migration and invasion abilities, and tumor growth in PC. TRIM46 overexpression also activated NF-κB signaling in PC cells. To sum up, ONECUT3 has been identified as a promising prognostic indicator in PC, and targeting this cancer-promoting pathway could offer an effective therapeutic approach to combat the PC progression.
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