Targeting insulin-like growth factor-binding protein-3 by microRNA-125b promotes tumor invasion and poor outcomes in non-small-cell lung cancer

Hsiu Hua Wang, Yao Chen Wang, De-Wei Wu, Chin Sheng Hung, Chih Yi Chen, Huei Lee

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Insulin-like growth factor-binding protein-3 acts as a tumor suppressor that inhibits the PI3K/AKT signaling pathway due to blocking insulin growth factor-1 binding to its receptor. We hypothesized that insulin-like growth factor-binding protein-3 might be targeted by microRNA-125b and promote tumor invasion and poor outcome in non-small-cell lung cancer via activation of the PI3K/AKT signaling pathway. Real-time polymerase chain reaction and immunohistochemistry were performed to determine the level of microRNA-125b, insulin-like growth factor-binding protein-3 messenger RNA, and phosphorylated-AKT expression in 105 tumors from non-small-cell lung cancer patients. Low insulin-like growth factor-binding protein-3 messenger RNA levels and positive phosphorylated-AKT expression were more commonly found in patients with high microRNA-125b tumors than low microRNA-125b tumors. A poorer overall survival and relapse-free survival were observed in patients with high microRNA-125b tumors than low-microRNA-125b tumors in p53-mutated patients, but not in p53-wild-type patients. Mechanistically, microRNA-125b promotes invasion ability in p53-mutated cells via the PI3K/AKT activation by targeting of insulin-like growth factor-binding protein-3, but this effect was not observed in p53-wild-type cells. An increase in phosphorylated-AKT expression due to targeting of insulin-like growth factor-binding protein-3 by microRNA-125b was responsible for cell invasion in p53-mutated cells. In conclusion, the microRNA-125b level promotes invasive ability in p53-mutated cells via PI3K/AKT activation by targeting of insulin-like growth factor-binding protein-3, thereby resulting in p53-mutated non-small-cell lung cancer patients with poor outcomes.

Original languageEnglish
JournalTumor Biology
Volume39
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Keywords

  • MicroRNA-125b
  • non-small-cell lung cancer
  • outcome
  • p53 mutation
  • tumor invasion

ASJC Scopus subject areas

  • Cancer Research

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