MicroRNA-7/NF-κB signaling regulatory feedback circuit regulates gastric carcinogenesis.
MicroRNAs play essential roles in gene expression regulation during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer (GC). We used genome-wide screenings and identified RELA and FOS as novel targets of miR-7. Overexpression of miR-7 repressed RELA and FOS expression and prevented GC cell proliferation and tumorigenesis. These effects were clinically relevant, as low miR-7 expression was correlated with high RELA and FOS expression and poor survival in GC patients. Intriguingly, we found that miR-7 indirectly regulated RELA activation by targeting the IκB kinase IKKε. Furthermore, IKKε and RELA can repress miR-7 transcription, which forms a feedback circuit between miR-7 and nuclear factor κB (NF-κB) signaling. Additionally, we demonstrate that down-regulation of miR-7 may occur as a result of the aberrant activation of NF-κB signaling by Helicobacter pylori infection. These findings suggest that miR-7 may serve as an important regulator in GC development and progression.
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Xiao-Di
XD
Zhao
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Yuan-Yuan
YY
Lu
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Hao
H
Guo
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Hua-Hong
HH
Xie
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China Department of Nephrology, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Li-Jie
LJ
He
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Gao-Fei
GF
Shen
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Jin-Feng
JF
Zhou
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Ting
T
Li
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Si-Jun
SJ
Hu
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Lin
L
Zhou
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Ya-Nan
YN
Han
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Shu-Li
SL
Liang
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Xin
X
Wang
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Kai-Chun
KC
Wu
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Yong-Quan
YQ
Shi
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Yong-Zhan
YZ
Nie
State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi 710032, China daimingfan@fmmu.edu.cn yongznie@fmmu.edu.cn shiyquan@fmmu.edu.cn.
Dai-Ming
DM
Fan
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D025461:Feedback, Physiological; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009368:Neoplasm Transplantation; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
D020413:3' Untranslated Regions; D051550:I-kappa B Kinase; D035683:MicroRNAs; D020543:Proteome; D016760:Proto-Oncogene Proteins c-fos; D051996:Transcription Factor RelA; C549242:MIRN7-1 microRNA, human; C498143:RELA protein, human