MicroRNA-143-3p, up-regulated in H. pylori-positive gastric cancer, suppresses tumor growth, migration and invasion by directly targeting AKT2

// Fang Wang 1 , Jiatao Liu 1, 2 , Yanfeng Zou 3 , Yang Jiao 1 , Yawei Huang 1 , Lulu Fan 1 , Xiaoqiu Li 1 , Hanqing Yu 1 , Chengqun He 4 , Wei Wei 5 , Hua Wang 1, 6, * , Guoping Sun 1, * 1 Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China 2 Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui, China 3 Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei 230032, Anhui, China 4 Department of Gynaecology and Obstetrics, Anhui Provincial Hospital, Hefei 230001, Anhui, China 5 Institute of Clinical Pharmacology, Anhui Medical University, Hefei 230032, Anhui, China 6 Institute for Liver Diseases of Anhui Medical University, Hefei 230032, Anhui, China * These authors have contributed equally to this work Correspondence to: Hua Wang, email: wanghua@ahmu.edu.cn Guoping Sun, email: sungp@ahmu.edu.cn Keywords: Helicobacter pylori , gastric cancer, microRNA-143-3p, AKT2, progression Received: May 23, 2016     Accepted: January 27, 2017     Published: February 23, 2017 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.