miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer.
Therapeutic applications of microRNA (miRNA) in KRAS-driven pancreatic cancers might be valuable, but few studies have explored this area. Here, we report that miR-96 directly targets the KRAS oncogene and functions as a tumor-suppressing miRNA in pancreatic cancer cells. Ectopic expression of miR-96 through a synthetic miRNA precursor inhibited KRAS, dampened Akt signaling, and triggered apoptosis in cells. In human clinical specimens, miR-96 was downregulated or deleted where an association with KRAS elevations was observed. In vitro and in vivo assays established that miR-96 decreased cancer cell invasion and migration and slowed tumor growth in a manner associated with KRAS downregulation. Our findings identify miR-96 as a potent regulator of KRAS, which may provide a novel therapeutic strategy for treatment of pancreatic cancer and other KRAS-driven cancers.
Yu
Shuangni
S
Department of Pathology, Peking Union Medical College Hospital, Tsinghua University, Beijing, PR China.
Lu
Zhaohui
Z
Liu
Changzheng
C
Meng
Yunxiao
Y
Ma
Yihui
Y
Zhao
Wugan
W
Liu
Jianping
J
Yu
Jia
J
Chen
Jie
J
D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D016147:Genes, Tumor Suppressor; D011905:Genes, ras; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009361:Neoplasm Invasiveness; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction; D014162:Transfection; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; C117307:KRAS protein, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D051058:Oncogene Protein v-akt; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins