title: The microRNA-423-3p-Bim Axis Promotes Cancer Progression and Activates Oncogenic Autophagy in Gastric Cancer.
abstract: Human serum microRNAs (miRNAs) have been shown to serve as disease fingerprints for predicting survival of cancer patients. However, the roles of specific miRNAs involved in gastric cancer (GC) are largely unknown. In this study, miRNA profiling was performed on sera obtained from six patients in good- and poor-survival groups. Expression of miR-423-3p was validated by quantitative RT-PCR in another 67 GC serum samples and paired normal and cancerous gastric tissues. Luciferase reporter assays were used to identify the target gene Bcl-2-interacting mediator of cell death (Bim). As a result, between the good-survival and poor-survival groups, the expression of nine serum miRNAs was altered more than two-fold. Among these, miR-423-3p was significantly increased in the poor-survival group, and its overexpression in GC tissues predicted poor survival in 119 patients with GC. miR-423-3p was found to promote cell proliferation, migration, and invasion in cell lines and animal models. Mechanistically, knockdown of the autophagy-related gene (Atg) 7 rescued the GC-promoting effect of miR-423-3p. In conclusion, miR-423-3p activates oncogenic and Beclin-1-dependent autophagy and promotes GC progression by reducing the expression of Bim. The newly identified miR-423-3p-Bim axis might be a potential therapeutic target in GC.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China; Department of the VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Hematology Oncology, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Qirong
authors.initials: Q
authors.lastname: Geng
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of the VIP Region, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Liangping
authors.initials: L
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China.
authors.forename: Youqing
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510006, China; Department of Gastric Surgery, Sun Yat-Sen University Cancer Center, Guangzhou 510006, China. Electronic address: xudzh@sysucc.org.cn.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Xu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics*; D000072224:Bcl-2-Like Protein 11 / Q000235:genetics*; D000071186:Beclin-1 / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D051379:Mice; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D011379:Prognosis; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000072224:Bcl-2-Like Protein 11; D000071186:Beclin-1; C548900:MIRN423 microRNA, human; D035683:MicroRNAs
keywords: Bim; autophagy; gastric cancer; microRNA-423-3p