Effects of microRNA-183 on epithelial-mesenchymal transition, proliferation, migration, invasion and apoptosis in human pancreatic cancer SW1900 cells by targeting MTA1

Exp Mol Pathol. 2017 Jun;102(3):522-532. doi: 10.1016/j.yexmp.2017.05.009. Epub 2017 May 12.

Abstract

Objective: This study aims to explore effects of miR-183 on epithelial-mesenchymal transition (EMT) and invasion by targeting MTA1 in human pancreatic cancer (PC) cells.

Methods: Totally, 108 PC patients admitted in Wenzhou Central Hospital and Wenzhou People's Hospital, The Dingli Clinical Institute of Wenzhou Medical University from March 2010 to March 2014 were enrolled. qRT-PCR and immunohistochemistry were applied to examine expression of MTA1 mRNA and protein. Samples were divided into 6 groups: blank, NC, miR-183 mimics, miR-183 inhibitors, MTA1-siRNA and miR-183 inhibitors +MTA1-siRNA groups. CCK8 method was employed for determining cell proliferation rate, flow cytometry for cell apoptosis rate, scratch test for cell migration and Transwell assay for cell invasion. qRT-PCR and Western blotting were used to determine expression of MTA1, E-cadherin and Vimentin mRNA and protein.

Results: Positive expression rate of MTA1 was upregulated in PC tissues, and expression of miR-183 and MTA1 was associated with differentiation, migration, tumor size, TNM. The miR-183 mimics and MTA1-siRNA groups showed a decrease in proliferation, migration and invasion, whereas increased apoptosis, in comparison with blank and NC groups, as expression of MTA1 and Vimentin mRNA and protein were reduced, expression of E-cadherin mRNA and protein was elevated. Compared to blank and NC groups, the miR-183 inhibitors group exhibited enhanced proliferation, migration and invasion and inhibited apoptosis; increased expressions of MTA1 and Vimentin mRNA and protein and decreased expressions of E-cadherin mRNA and protein.

Conclusion: Our study supported that miR-183 could repress EMT and invasion of human PC cells through inhibition of MTA1 expression.

Keywords: Epithelial-mesenchymal transition; Invasion; MTA1; Migration; Pancreatic cancer; microRNA-183.

MeSH terms

  • Antigens, CD
  • Apoptosis
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Gene Targeting
  • Histone Deacetylases / genetics*
  • Histone Deacetylases / metabolism
  • Humans
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / pathology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Repressor Proteins / antagonists & inhibitors
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Trans-Activators
  • Up-Regulation
  • Vimentin / genetics
  • Vimentin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • MIRN183 microRNA, human
  • MicroRNAs
  • MTA1 protein, human
  • RNA, Messenger
  • Repressor Proteins
  • Trans-Activators
  • Vimentin
  • Histone Deacetylases