title: Aquaporin 3 facilitates tumor growth in pancreatic cancer by modulating mTOR signaling.
abstract: Aquaporins (AQP) have been demonstrated to be dysregulated in many human cancers and is thought to be involved in pancreatic carcinogenesis and progression. However, the oncogenic roles and underlying mechanism of AQP in pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. In this study, by data mining of TCGA dataset and CCLE database, we identified that AQP3 is the major AQP expressed in PDAC. Then, the microRNA-874, was demonstrated to be a key regulator of AQP3 expression in PDAC cells. Genetic silencing of AQP3 expression had pronounced effects on cell proliferation and apoptosis of the PDAC cell lines BXPC3 and HPAFII. Introduction of microRNA-874 suppressed cell proliferation and promoted cell apoptosis, whereas inhibition of microRNA-874 had the opposite effect. Mechanistically, by a large-scale proteomic analysis, we revealed that AQP3 was significantly associated the activity of mTOR signaling. Moreover, modulation of AQP3 or microRNA-874 altered mTOR activity as demonstrated by the phosphorylation level of mTOR and its downstream target S6. Taken together, our data, as a proof of principle, suggest that AQP3 can promote tumor growth of pancreatic cancer cells by activating the Mtor signaling pathway and provide a potential therapeutic target in the treatment of PDAC.
authors.affiliation: School of Life Sciences, Fudan University, Shanghai 200433, PR China.
authors.forename: Xunwei
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Materials Science and Engineering, Shanghai Key Laboratory of D&A for Metal-Functional Materials, Tongji University, Shanghai 201804, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Personal Health (Shanghai) Co., Ltd, Shanghai 200433, PR China. Electronic address: shaomh@personalhealth.com.cn.
authors.forename: Minhua
authors.initials: M
authors.lastname: Shao
mesh_terms: D017209:Apoptosis; D051400:Aquaporin 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C496027:AQP3 protein, human; C561946:MIRN874 microRNA, human; D035683:MicroRNAs; D051400:Aquaporin 3; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: AQP3; Pancreatic cancer; mTOR signaling; microRNA-874