Hsa-miR-623 suppresses tumor progression in human lung adenocarcinoma

Cell Death Dis. 2016 Sep 29;7(9):e2388. doi: 10.1038/cddis.2016.260.

Abstract

Our previous study revealed that Ku80 was overexpressed in lung cancer tissues and hsa-miR-623 regulated the Ku80 expression; however, the detailed function of hsa-miR-623 in lung cancer was unclear. We identified that hsa-miR-623 bound to the 3'-UTR of Ku80 mRNA, thus significantly decreasing Ku80 expression in lung adenocarcinoma cells. Hsa-miR-623 was downregulated in lung adenocarcinoma tissues compared with corresponding non-tumorous tissues, and its expression was inversely correlated with Ku80 upregulation. Downregulation of hsa-miR-623 was associated with poor clinical outcomes of lung adenocarcinoma patients. Hsa-miR-623 suppressed lung adenocarcinoma cell proliferation, clonogenicity, migration and invasion in vitro. Hsa-miR-623 inhibited xenografts growth and metastasis of lung adenocarcinoma in vivo. Ku80 knockdown in lung adenocarcinoma cells suppressed tumor properties in vitro and in vivo similar to hsa-miR-623 overexpression. Further, hsa-miR-623 overexpression decreased matrix metalloproteinase-2 (MMP-2) and MMP-9 expression levels, with decreased ERK/JNK phosphorylation. Inhibition of hsa-miR-623 or overexpression of Ku80 promoted lung adenocarcinoma cell invasion, activated ERK/JNK phosphorylation and increased MMP-2/9 expressions, which could be reversed by ERK kinase inhibitor or JNK kinase inhibitor. In summary, our results showed that hsa-miR-623 was downregulated in lung adenocarcinoma and suppressed the invasion and metastasis targeting Ku80 through ERK/JNK inactivation mediated downregulation of MMP-2/9. These findings reveal that hsa-miR-623 may serve as an important therapeutic target in lung cancer therapy.

Publication types

  • Retracted Publication

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Animals
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Ku Autoantigen / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • MAP Kinase Signaling System
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Treatment Outcome
  • Xenograft Model Antitumor Assays

Substances

  • MIRN623 microRNA, human
  • MicroRNAs
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Ku Autoantigen