miR-511-5p Suppresses Cell Migration, Invasion and Epithelial-Mesenchymal Transition Through Targeting PAK2 in Gastric Cancer

Biochem Genet. 2022 Jun;60(3):899-913. doi: 10.1007/s10528-021-10126-y. Epub 2021 Sep 20.

Abstract

As a malignant tumor, gastric cancer (GC) is closely related with gastric mucosa and has a high mortality in the world. Since microRNA (miRNA) has become more and more important in tumor research, we intend to find out the functional role and mechanism of miR-511-5p in GC. Firstly, miR-511-5p level was examined in human GC cell lines and tissues, and its effect on cell migration and invasion of BGC-823 or HGC-27 cells was tested by migration assay and transwell assay. Then, we confirmed the association between miR-511-5p and p21 activated kinase 2 (PAK2) by the luciferase reporter assay, and further assessed their role in cell migration and invasion. Moreover, we verified the function of miR-511-5p and PAK2 in epithelial-mesenchymal transition (EMT). In our study, miR-511-5p was downregulated in GC cell lines and tissues, and inversely associated with PAK2. Luciferase reporter assay confirmed that miR-511-5p could bind to PAK2. MiR-511-5p mimics significantly upregulated E-cadherin and downregulated N-cadherin, Vimentin and Snail, and consequently inhibited cell migration and invasion. However, reintroduction of PAK2 reversed the inhibitory function of miR-511-5p on BGC-823 and HGC-27 cells. Our research suggested that tumor-suppressive function of miR-511-5p in GC was inhibited by PAK2, and miR-511-5p/PAK2 axis may serve as a new strategy in GC management.

Keywords: Cell migration and invasion; EMT; Gastric cancer; PAK2; miR-511-5p.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Neoplasm Invasiveness / genetics
  • Stomach Neoplasms* / pathology
  • p21-Activated Kinases / genetics
  • p21-Activated Kinases / metabolism
  • p21-Activated Kinases / pharmacology

Substances

  • MIRN511 microRNA, human
  • MicroRNAs
  • PAK2 protein, human
  • p21-Activated Kinases