MiR-424 Promotes Non-Small Cell Lung Cancer Progression and Metastasis through Regulating the Tumor Suppressor Gene TNFAIP1

Cell Physiol Biochem. 2017;42(1):211-221. doi: 10.1159/000477314. Epub 2017 May 25.

Abstract

Background/aims: This study aimed to investigate the potential roles of miR-424 expression in non-small cell lung cancer (NSCLC) metastasis and growth and its underlying mechanism.

Methods: The expression of miR-424 in two NSCLC cell lines (A549 and H1975) was altered by transfection with miR-424 mimic and inhibitor. Effects of miR-424 overexpression and suppression on cells migration, invasion and colony formation were analyzed. Target genes for miR-424 were predicted using bioinformatics method and then verified using luciferase assay. Effects of miR-424 expression on cell migration, invasion and proliferation were reanalyzed on the condition of TNFAIP1 was silenced. Moreover, TNFAIP1 silencing and miR-424 modified A549 cells were subcutaneous injected into node BALB/c mice to confirm the regulation of miR-424 on TNFAIP1 in regulating tumor growth.

Results: Compared with the control, miR-424 overexpression significantly increased the migrated and invaded cells, as well as the proliferated colonies. TNFAIP1 was a predicted target gene for miR-424, and was negatively regulated by miR-424. TNFAIP1 silence significantly increased the migrated and invaded cells compared to that in control, while these increases were abolished by miR-424 suppression. Animal experiment further evidenced miR-424 affected tumor growth by regulating TNFAIP1.

Conclusions: These data demonstrate that miR-424 may be a contributor for NSCLC progression and metastasis through involving in cell migration, invasion and proliferation via inhibiting TNFAIP1. This study may provide theoretical basis for miR-424 in NSCLC target therapeutic treatment.

Keywords: Cell migration and invasion; Non-small cell lung cancer (NSCLC); TNFAIP1; miR-424.

Publication types

  • Retracted Publication

MeSH terms

  • 3' Untranslated Regions
  • A549 Cells
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antagomirs / metabolism
  • Base Sequence
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Proteins / antagonists & inhibitors
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Sequence Alignment
  • Transplantation, Heterologous

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Antagomirs
  • MIRN424 microrna, human
  • MicroRNAs
  • Proteins
  • RNA, Small Interfering
  • TNFAIP1 protein, human