title: MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses tumor growth, migration and invasion by directly targeting AKT2.
abstract: Our previous studies have suggested a protective role for H. pylori infection in the prognosis of gastric cancer. Based on those findings, we hypothesized that H. pylori-positive and -negative gastric cancers may exhibit different growth patterns and pathobiological behaviors, indicating different mechanisms of cancer progression. By microarray analysis, we studied miRNAs expression profiles in 42 gastric cancer patients, comparing 21 H. pylori-positive and 21 H. pylori-negative groups. Luciferase reporter assay and western blot were used to examine the potential target genes of the interested miRNA. In the present study, 53 miRNAs were significantly differentially expressed in H. pylori-positive and -negative gastric cancer tissues. We investigated the expression and function of one candidate, miR-143-3p, which was the most significantly increased miRNA in H. pylori-positive gastric cancer tissues. We observed that miR-143-3p expression was significantly decreased in gastric cancer tissues and cells, which correlated with late stage and lymph node metastasis. Using gain- and loss-of-function experiments in vitro, we demonstrate that miR-143-3p negatively regulated cell growth, apoptosis, migration and invasion. We further characterized AKT2 as a novel direct target of miR-143-3p. Knockdown of AKT2 expression mimicked the effects of miR-143-3p restoration. In conclusion, our data suggest that miR-143-3p acts as a novel tumor suppressive miRNA by regulating tumor growth, migration and invasion through directly targeting AKT2 gene. Further investigation is warranted to characterize the mechanisms underlying gastric cancer progression and may eventually contribute to its therapy.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.|Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Jiatao
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Xiaoqiu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Gynaecology and Obstetrics, Anhui Provincial Hospital, Hefei 230001, Anhui, China.
authors.forename: Chengqun
authors.initials: C
authors.lastname: He
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.|Institute for Liver Diseases of Anhui Medical University, Hefei 230032, Anhui, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China.
authors.forename: Guoping
authors.initials: G
authors.lastname: Sun
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D016480:Helicobacter pylori / Q000502:physiology*; D006801:Humans; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C542359:MIRN143 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT2; Helicobacter pylori; gastric cancer; microRNA-143-3p; progression