A team of scientists led by Prof. LIU Mofang at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, and Prof LOU Wenhui at Department of Pancreatic Surgery, Zhong Shan Hospital, have found that miR-489 mediates KRAS-driven pancreatic cancer metastasis. This work entitled “KRAS-NFκB-YY1-miR-489 signaling axis controls pancreatic cancer metastasis” was online published in Cancer Research on November 1, 2016. The work was collaborated with Drs. Li Yong, Liu Yingbin, and Li Dangsheng.
Pancreatic ductal adenocarnoma (PDAC), also known as pancreatic cancer, is one of the most lethal malignant tumors, with a 5-year survival rate less than 8%. Oncogenic KRAS mutation, occurring in over 90% of PDAC, has been validated as the driver mutation for PDAC progression and metastasis, but the underlying mechanisms involved in these processes are still poorly understood.
Yuan Peng, Xiaohong He, Yefei Rong and their colleagues, under the supervision of Drs. LIU Mofang and LOU Wenhui, found that 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, their results establish a pivotal mechanism of PDAC metastasis and suggest miR-489 a promising therapeutic candidate to target PDAC metastasis.
This study was supported by the grants from the Chinese Academy of Sciences, National Natural Science Foundation of China, Ministry of Science and Technology, and Science and Technology Commission of Shanghai Municipality.
KEYWORDS：miR-489; KRAS mutation; NF-kB; YY1; ADAM9; MMP7; Pancreatic ductal adenocarcinoma; metastasis
AUTHOR CONTACT:
LIU Mofang
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences,
Shanghai, China
Phone: 86-21-54921146;
E-mail: mfliu@sibcb.ac.cn
Article Link：http://cancerres.aacrjournals.org/cgi/content/abstract/0008-5472.CAN-16-1898
A model of miR-489 as a key regulatory node linking oncogenic KRAS mutations to PDAC metastasis. (Image provided by Dr. LIU Mofang)
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