MicroRNA-130a-3p suppresses cell migration and invasion by inhibition of TBL1XR1-mediated EMT in human gastric carcinoma

Mol Carcinog. 2018 Mar;57(3):383-392. doi: 10.1002/mc.22762. Epub 2017 Nov 19.

Abstract

MiR-130a-3p was found to play tumor suppressor role in most human cancers, except for gastric cancer. However, in this study, we demonstrated that miR-130a-3p was significantly down-regulated in gastric carcinoma (GC) tissues compared with adjacent non-neoplastic tissues, and decreased miR-130a-3p expression was associated with shorter overall survival (OS) and was an independent prognostic factor for OS in GC patients. Over-expression of miR-130a-3p remarkably inhibited not only GC cell migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, but also tumorigenesis and lung metastasis in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Conversely, inhibition of miR-130a-3p resulted in opposite phenotype changes in GC cells. Furthermore, TBL1XR1 was identified as a direct target of miR-130a-3p, and reintroduction of TBL1XR1 into miR-130a-3p-transfected MGC-803 cells reversed the inhibitory effects of miR-130a-3p on GC cell migration, invasion and EMT. Taken together, our data suggested that miR-130a-3p suppressed aggressive phenotype of GC cells partially by direct targeting and decreasing TBL1XR1 and subsequent EMT process.

Keywords: EMT; TBL1XR1; gastric cancer; metastasis; miR-130a-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Chick Embryo
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Nuclear Proteins / genetics*
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Repressor Proteins / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • MIRN130 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Repressor Proteins
  • TBL1XR1 protein, human