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Updated: Mar 12, 2026

Oncogene Expression Analysis with Alterations in pH in a Pancreatic Ductal Cell Line
Published on: April 11, 2025
KRAS/NF-κB/YY1/miR-489 Signaling Axis Controls Pancreatic Cancer Metastasis
Peng Yuan1,2, Xiao-Hong He1,2, Ye-Fei Rong3
1Center for RNA Research, State Key Laboratory of Molecular Biology-University of Chinese Academy of Sciences, CAS Center for Excellence in Molecular Cell Science, Shanghai, China.
Abstract:
KRAS activation occurring in more than 90% of pancreatic ductal adenocarcinomas (PDAC) drives progression and metastasis, but the underlying mechanisms involved in these processes are still poorly understood. Here, we show how KRAS acts through inflammatory NF-κB signaling to activate the transcription factor YY1, which represses expression of the tumor suppressor gene miR-489. In PDAC cells, repression of miR-489 by KRAS signaling inhibited migration and metastasis by targeting the extracellular matrix factors ADAM9 and MMP7. miR-489 downregulation elevated levels of ADAM9 and MMP7, thereby enhancing the migration and metastasis of PDAC cells. Together, our results establish a pivotal mechanism of PDAC metastasis and suggest miR-489 as a candidate therapeutic target for their attack. Cancer Res; 77(1); 100-11. ©2016 AACR.
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