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Tumor Biology

, Volume 37, Issue 4, pp 5185–5192 | Cite as

Critical role of miR-155/FoxO1/ROS axis in the regulation of non-small cell lung carcinomas

  • Likun Hou
  • Jian Chen
  • Yuhui Zheng
  • Chunyan Wu
Original Article

Abstract

Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung carcinomas (NSCLC) account for 85 % of lung cancer cases. Despite enormous achievement in the treatment of NSCLC, the molecular mechanisms underlying the pathogenesis are largely unknown. The current study was designed to evaluate the role of miR-155 in NSCLC cell proliferation and to explore the possible molecular mechanisms. We found that miR-155 expression was increased in NSCLC tissues and cell lines. The increase of miR-155 significantly increased A549 cell proliferation, decreased S phase cell population and increased G2/M phase cell population. Decrease of miR-155 expression markedly inhibited cell proliferation, increased S phase cell population, and decreased G2/M phase cell population. Increase of miR-155 significantly decreased forkhead box protein O1 (FoxO1) 3’UTR luciferase activity and expression and decrease of miR-155 notably increased FoxO1 expression. Overexpression of FoxO1 significantly inhibited miR-155-exerted increase of cell proliferation and G2/M cell population. Downregulation of FoxO1 by siRNAs significantly promoted cell proliferation, decreased S phase cell numbers, and increased G2/M cell population. Downregulation of FoxO1 markedly increased ROS level, as reflected by increased DHE staining. Moreover, when N-acetylcysteine was present, increase of cell proliferation induced by downregulation of FoxO1, and upregulation of miR-155 was significantly inhibited. In conclusion, we found that miR-155 promoted NSCLC cell proliferation through inhibition of FoxO1 and the subsequent increase of ROS generation. Our findings highlight miR-155/FoxO1/ROS axis as a novel therapeutic target for the inhibition of NSCLC growth.

Keywords

miR-155 Forkhead box protein O1 Reactive oxygen species Non-small cell lung carcinomas Cell proliferation 

Abbreviations

FoxO1

forkhead box protein O1

NAC

N-acetylcysteine

NSCLC

non-small cell lung carcinomas

ROS

reactive oxygen species

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

13277_2015_4335_MOESM1_ESM.docx (72 kb)
Supplemental Fig. 1 (DOCX 71 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Pathology, Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina
  2. 2.Department of RadiologyShanghai Construction Group HospitalShanghaiChina
  3. 3.Department of PathologyFujian Medical University HospitalFuzhouChina

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