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Molecular Cancer
Published in: Molecular Cancer 1/2019

Open Access 01-12-2019 | Lung Cancer | Research

Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer

Authors: Juze Yang, Qiongzi Qiu, Xinyi Qian, Jiani Yi, Yiling Jiao, Mengqian Yu, Xufan Li, Jia Li, Chunyi Mi, Jisong Zhang, Bingjian Lu, Enguo Chen, Pengyuan Liu, Yan Lu

Published in: Molecular Cancer | Issue 1/2019

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Abstract

Introduction

Long noncoding RNAs (lncRNAs) are emerging as key players in the development and progression of cancer. However, the biological role and clinical significance of most lncRNAs in lung carcinogenesis remain unclear. In this study, we identified and explored the role of a novel lncRNA, lung cancer associated transcript 1 (LCAT1), in lung cancer.

Methods

We predicted and validated LCAT1 from RNA-sequencing (RNA-seq) data of lung cancer tissues. The LCAT1–miR-4715-5p–RAC1 axis was assessed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Signaling pathways altered by LCAT1 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT1 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro.

Results

LCAT1 is an oncogene that is significantly upregulated in lung cancer tissues and associated with poor prognosis. LCAT1 knockdown caused growth arrest and cell invasion in lung cancer cells in vitro, and inhibited tumorigenesis and metastasis in the mouse xenografts. Mechanistically, LCAT1 functions as a competing endogenous RNA for miR-4715-5p, thereby leading to the upregulation of the activity of its endogenous target, Rac family small GTPase 1 (RAC1). Moreover, EHop-016, a small molecule inhibitor of RAC1, as an adjuvant could improve the Taxol monotherapy against lung cancer cells in vitro.

Conclusions

LCAT1–miR-4715-5p–RAC1/PAK1 axis plays an important role in the progression of lung cancer. Our findings may provide valuable drug targets for treating lung cancer. The novel combination therapy of Taxol and EHop-016 for lung cancer warrants further investigation, especially in lung cancer patients with high LCAT1 expression.
Appendix
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Metadata
Title
Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer
Authors
Juze Yang
Qiongzi Qiu
Xinyi Qian
Jiani Yi
Yiling Jiao
Mengqian Yu
Xufan Li
Jia Li
Chunyi Mi
Jisong Zhang
Bingjian Lu
Enguo Chen
Pengyuan Liu
Yan Lu
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2019
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-019-1107-y

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