LncRNA H19 promotes epithelial-mesenchymal transition (EMT) by targeting miR-484 in human lung cancer cells

J Cell Biochem. 2018 Jun;119(6):4447-4457. doi: 10.1002/jcb.26537. Epub 2018 Mar 1.

Abstract

Recently, the long non-coding RNA (lncRNA) H19 has been identified as an oncogenic gene in multiple cancer types. However, the molecular basis for this observation has not been characterized in lung cancer, especially during epithelial mesenchymal transition (EMT) progression. Cell viability, migration, invasion, and apoptosis were measured using trypan blue exclusion assay, Transwell migration/invasion assay, and flow cytometry, respectively. Quantitative RT-PCR was used to measure relative expressions of H19, microR-484 (miR-484), and Rho associated coiled-coil containing protein kinase 2 (ROCK2). Western blot was used to measure expressions of apoptosis-, EMT-, and c-Jun N-terminal kinase (JNK) pathway-related proteins. Luciferase reporter assay was used to identify the target of H19. H19 was highly expressed in both lung cancer tissues and cells. Suppression of H19 significantly decreased A549 cell viability, migration, and invasion, but promoted apoptosis. Overexpression of H19 promoted cell migration, invasion, and EMT process. miR-484 was a target of H19 and overexpression of it reversed the effects of H19 on EMT. miR-484 regulated the expression of ROCK2. Mechanistic study revealed that suppressing H19 decreased the expression of proteins in JNK pathway, and ROCK2 was the main downstream molecule of H19. H19 promoted EMT in lung cancer A549 cells by negatively regulating miR-484.

Keywords: JNK pathway; LncRNA H19; ROCK2; epithelial-mesenchymal transition; lung cancer cells; miR-484.

Publication types

  • Retracted Publication

MeSH terms

  • A549 Cells
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Invasiveness
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Long Noncoding / biosynthesis*
  • RNA, Long Noncoding / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism

Substances

  • H19 long non-coding RNA
  • MIRN484 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • RNA, Neoplasm
  • ROCK2 protein, human
  • rho-Associated Kinases
  • MAP Kinase Kinase 4