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Published in: Cancer Cell International 1/2019

Open Access 01-12-2019 | Primary research

PITX2 enhances progression of lung adenocarcinoma by transcriptionally regulating WNT3A and activating Wnt/β-catenin signaling pathway

Authors: Jing Luo, Yu Yao, Saiguang Ji, Qi Sun, Yang Xu, Kaichao Liu, Qiang Diao, Yong Qiang, Yi Shen

Published in: Cancer Cell International | Issue 1/2019

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Abstract

Background

The homeodomain transcription factor, PITX2 is associated with tumorigenesis of multiple cancers. In this research, we aimed to study the expression, function and mechanism of PITX2 in lung adenocarcinoma (LUAD).

Methods

The TCGA dataset was used to analyze the expression and clinical significance of PITX2 in LUAD. The expression of PITX2 in tumor samples and LUAD cell lines was examined by quantitative real-time PCR (qRT-PCR) and western blotting. Small interfering RNAs (siRNAs) were constructed to knockdown PITX2 and to determine the physiological function of PITX2 in vitro. Xenograft model was used to confirm the role of PITX2 in vivo.

Results

PITX2 was overexpressed in LUAD and patients with high level of PITX2 had a worse overall survival and an advanced clinical stage. Knockdown of PITX2 inhibited cell proliferation, migration and invasion of LUAD cells. Further study revealed that the oncogenic role of PITX2 was dependent on activating Wnt/β-catenin signaling pathway, especially by transcriptionally regulating the Wnt gene family member, WNT3A. Lastly, we identified miR-140-5p as a negative mediator of PITX2 by binding its 3′UTR and ectopic expression of miR-140-5p inhibited progression of LUAD cells via suppressing the expression of PITX2.

Conclusions

Up-regulation of PITX2 acts as an oncogene in LUAD by activating Wnt/β-catenin signaling pathway, suggesting that PITX2 may serve as a novel diagnostic and prognostic biomarker in LUAD.
Appendix
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Metadata
Title
PITX2 enhances progression of lung adenocarcinoma by transcriptionally regulating WNT3A and activating Wnt/β-catenin signaling pathway
Authors
Jing Luo
Yu Yao
Saiguang Ji
Qi Sun
Yang Xu
Kaichao Liu
Qiang Diao
Yong Qiang
Yi Shen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2019
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-019-0800-7

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