title: PRL-3 promotes gastric cancer migration and invasion through a NF-κB-HIF-1α-miR-210 axis.
abstract: Phosphatase of regenerating liver-3 (PRL-3) has been implicated in controlling cancer cell invasiveness. Deregulated expression of PRL-3 is involved in cancer progression and predicts poor overall survival. Recent studies have revealed critical roles for microRNAs in various cellular processes, including tumorigenic development. In this study, we aimed to explore the linkage between PRL-3 and microRNAs in gastric cancer. We found that PRL-3 transcript levels were positively correlated with miR-210 levels in gastric cancer tissues. In gastric cancer cells, PRL-3 upregulated miR-210 expression in a HIF-1α-dependent fashion under normoxia and hypoxia. In addition, PRL-3 activated NF-κB signaling and promoted HIF-1α expression through modulating phosphorylation of p65. NF-κB signaling, HIF-1α, and miR-210 partially contributed to PRL-3-induced migration and invasion. Furthermore, the levels of PRL-3, HIF-1α, and miR-210 transcripts inversely affected the overall survival of gastric cancer patients. Our work identified the existence of a PRL-3-NF-κB-HIF-1α-miR-210 axis, thus providing new insight into the role of PRL-3 in promoting gastric cancer invasiveness.
  
  
  CONCLUSIONS
  PRL-3 regulates microRNA in gastric cancer. PRL-3 elevates hsa-miR-210 by upregulating HIF-1α. PRL-3 activates a NF-κB-HIF-1α-miR-210 axis by enhancing the phosphorylation of p65. PRL-3 promotes cell migration and invasion via the NF-κB-HIF-1α-miR-210 axis. High levels of PRL-3 and miR-210 are related with poor OS in gastric cancer.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing, 100142, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing, 100142, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing, 100142, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Meng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing, 100142, China.
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Beijing, 100142, China. Chengchaoshou@outlook.com.
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002465:Cell Movement; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C543800:MIRN210 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: Gastric cancer invasiveness; HIF-1α; Hypoxia; NF-κB signaling; PRL-3; miR-210