title: miR 1296-5p Inhibits the Migration and Invasion of Gastric Cancer Cells by Repressing ERBB2 Expression.
abstract: The metastasis of gastric cancer, one of the most common tumors, has a molecular mechanism that is still largely unclear. Here we investigated the role of possible tumor-suppressor miR-1296-5p in the cell migration and invasion of ERBB2-positive gastric cancer. It found that miR-1296-5p was significantly down-regulated in gastric cancer tissues. Moreover, it was down-regulated in lymph node metastatic gastric cancer tissues compared with non-metastatic gastric cancer tissues. The luciferase activity of ERBB2 3'-untranslated region-based reporters constructed in SNU-216 and NUGC-4 gastric cancer cells suggested that ERBB2 was the target gene of miR-1296-5p. Overexpressed miR-1296-5p reduced its target protein level and Rac1 activation, and inhibited the migration and invasion of SNU-216 and NUGC-4 gastric cancer cells. MiR-1296-5p was down-regulated in ERBB2-positive gastric cancer tissues compared with ERBB2-negative gastric cancer tissues. In ERBB2-positive gastric cancers, the miR-1296-5p expression was suppressed in a majority of metastatic lymph node tissues compared to non-metastatic gastric cancer samples. The migration and invasion of gastric cancer cells was inhibited by miR-1296-5p overexpression or herceptin treatment, and rescued by the overexpression of constitutively active Rac1-Q61L or ERBB2. Taken together, our findings first suggest that miR-1296-5p might be involved in the regulation on the migration and invasion of human gastric cancer cells at least in part via targeting ERBB2/Rac1 signaling pathway.
authors.affiliation: Department of Respiration, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Shan
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.affiliation: Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, PR China.
authors.forename: Danxia
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Safety Assessment and Research Center for Drug, Pesticide and Veterinary Drug of Jiangsu Province, Nanjing Medical University, Nanjing, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yan
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Zebo
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Huo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Tongshan
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Nanjing Medical University, Nanjing, PR China.|State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, PR China.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Jiangsu Cancer Hospital, Nanjing, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008207:Lymphatic Metastasis / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000473:pathology*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D008156:Luciferases; D035683:MicroRNAs; D018719:Erb-b2 Receptor Tyrosine Kinases; D020830:rac1 GTP-Binding Protein; C000621896:MIRN-1296 microRNA, human; C107953:RAC1 protein, human; C508053:ERBB2 protein, human