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© 2017. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
Targeting insulin-like growth factor-binding protein-3 by microRNA-125b promotes tumor invasion and poor outcomes in non-small-cell lung cancer
Author
Wang, Hsiu-Hua 1 ; Yao-Chen, Wang 2 ; De-Wei, Wu 1 ; Chin-Sheng, Hung 3 ; Chen, Chih-Yi 4 ; Lee, Huei 1 

 Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan 
 Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan 
 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University Hospital, Taipei, Taiwan; Division of General Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan; Cancer Research Center, Taipei Medical University Hospital, Taipei, Taiwan 
 Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan 
Publication year
2017
Publication date
Apr 2017
Publisher
Sage Publications Ltd.
ISSN
10104283
e-ISSN
14230380
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2113710872
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.