journal contribution posted on 2023-03-31, 00:28 authored by Peng Yuan, Xiao-Hong He, Ye-Fei Rong, Jing Cao, Yong Li, Yun-Ping Hu, Yingbin Liu, Dangsheng Li, Wenhui Lou, Mo-Fang Liu
This file contains 6 figures (Supplementary Fig. S1-6) and 1 table (Supplementary Table S1). These figures and table provide additional, directly relevant, and unrepeated information for the article content. In brief, Supplementary Figures S1 and S3 indicate that miR-489 is an effector downstream of KRAS signaling; Supplementary Figures S2 and S5 show that miR-489:ADAM9/MMP7 axis doesn't confer the cell proliferation regulation of KRAS signaling; Supplementary Figure S4 highlights the promoting function of ADAM9 and MMP7 in PDAC metastasis; Supplementary Figure S6 is the additional information of Figure 6 in the main text; and Supplementary Table S1 shows the sequences of chemically synthesized DNA and RNA oligonucleotides. These data are equal in quality and presentation to materials within the main article.
National Natural Science Foundation of China
Ministry of Science and Technology of China
Science and Technology Commission of Shanghai Municipality
Chinese Academy of Sciences
ARTICLE ABSTRACTKRAS 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.