title: Gastric Cancer Cell Proliferation and Survival Is Enabled by a Cyclophilin B/STAT3/miR-520d-5p Signaling Feedback Loop.
abstract: Molecular links between inflammation and cancer remain obscure despite their great pathogenic significance. The JAK2/STAT3 pathway activated by IL6 and other proinflammatory cytokines has garnered attention as a pivotal link in cancer pathogenesis, but the basis for its activation in cancer cells is not understood. Here we report that an IL6-triggered feedback loop involving STAT3-mediated suppression of miR-520d-5p and upregulation of its downstream target cyclophilin B (CypB) regulate the growth and survival of gastric cancer cells. In clinical specimens of gastric cancer, we documented increased expression of CypB and activation of STAT3. Mechanistic investigations identified miR-520d-5p as a regulator of CypB mRNA levels. This signaling axis regulated gastric cancer growth by modulating phosphorylation of STAT3. Furthermore, miR-520d-5p was identified as a direct STAT3 target and IL6-mediated inhibition of miR-520d-5p relied upon STAT3 activity. Our findings define a positive feedback loop that drives gastric carcinogenesis as influenced byH. pyloriinfections that involve proinflammatory IL6 stimulation.Cancer Res; 77(5); 1227-40. ©2016 AACR.
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.|Department of Gastroenterology, The 264 Hospital of PLA, Taiyuan, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.|Department of Gastroenterology, Xi'an Central Hospital, College of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.|Department of Oncology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. daimingfan@fmmu.edu.cn shiyquan@fmmu.edu.cn.
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Xijing Hospital, The Fourth Military Medical University, Xi'an, China. daimingfan@fmmu.edu.cn shiyquan@fmmu.edu.cn.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D021983:Cyclophilins / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D014162:Transfection
chemical_list: C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C081786:cyclophilin B; D021983:Cyclophilins