title: miR-181a-5p promotes the progression of gastric cancer via RASSF6-mediated MAPK signalling activation.
abstract: We previously discovered that Ras association domain family member 6 (RASSF6) was downregulated and predicted poor prognosis in GC patients. However, the mechanisms of the down regulation of RASSF6 in GC remained unclear. Increasing evidence indicates that dysregulation of microRNAs promotes the progression of cancer through the repression of tumour suppressors. Here, we identified miR-181a-5p as a novel regulator of RASSF6 in GC. Functionally, ectopic expression or silencing of miR-181a-5p, respectively, promoted or inhibited GC cell proliferation, colony formation and cell cycle transition, as well as enhanced or prevented the invasion, metastasis of GC cells and epithelial to mesenchymal transition of GC cells in vitro and in vivo. Molecularly, miR-181a-5p functioned as an onco-miRNA by activating the RASSF6-regulated MAKP pathway. Overexpression or silencing of RASSF6 could partially reverse the effects of the overexpression or repression of miR-181a-5p on GC progress caused by activation of the MAKP pathway in vitro and in vivo. Clinically, high miR-181a-5p expression predicted poor survival in GC patients, especially combined with low RASSF6 expression. Collectively, we identified miR-181a-5p as an onco-miRNA, which acts by directly repressing RASSF6 in GC.
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: miyushuai@sina.com.
authors.forename: Yushuai
authors.initials: Y
authors.lastname: Mi
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: sjtuzdy@sina.com.
authors.forename: Dongyuan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: docjiangwl@163.com.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: JEROME6694@163.com.
authors.forename: Junyong
authors.initials: J
authors.lastname: Weng
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: cz-zhou@163.com.
authors.forename: Chongzhi
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: huangkejianshgh@163.com.
authors.forename: Kejian
authors.initials: K
authors.lastname: Huang
authors.affiliation: Department of Pathology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: huameitd@hotmail.com.
authors.forename: Huamei
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: yyfd89@126.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: xishengsd@126.com.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Electronic address: cuiweiyingqi@hotmail.com.
authors.forename: Weiyingqi
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Pathology, Shanghai Cancer Center, Fudan University, Shanghai, China. Electronic address: doctzm@163.com.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Linköping University, Linköping, Sweden; Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Electronic address: xiaofeng_sun58@126.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China. Electronic address: zhouzzghuaxi@163.com.
authors.forename: Zongguang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: pengpzhh@hotmail.com.
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: sunshinezsl1989@163.com.
authors.forename: Senlin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. Electronic address: wenyugang1502@sina.com.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wen
mesh_terms: D051017:Apoptosis Regulatory Proteins; D049109:Cell Proliferation; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology*; D035683:MicroRNAs / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology*; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000209:etiology* / Q000401:mortality / Q000473:pathology
chemical_list: D051017:Apoptosis Regulatory Proteins; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; C519911:RASSF6 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: Gastric cancer progression; MAPK; RASSF6; miR-181a-5p