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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Radiotherapy | Research

LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway

Authors: Xiao-Ya Sun, Hao-Zheng Li, Da-Fei Xie, Shan-Shan Gao, Xin Huang, Hua Guan, Chen-Jun Bai, Ping-Kun Zhou

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

Background

Epithelial-to-mesenchymal transition (EMT) is a critical event contributing to more aggressive phenotypes in cancer cells. EMT is frequently activated in radiation-targeted cells during the course of radiotherapy, which often endows cancers with acquired radioresistance. However, the upstream molecules driving the signaling pathways of radiation-induced EMT have not been fully delineated.

Methods

In this study, RNA-seq-based transcriptome analysis was performed to identify the early responsive genes of HeLa cells to γ-ray irradiation. EMT-associated genes were knocked down by siRNA technology or overexpressed in HeLa cells and A549 cells, and the resulting changes in phenotypes of EMT and radiosensitivity were assessed using qPCR and Western blotting analyses, migration assays, colony-forming ability and apoptosis of flow cytometer assays.

Results

Through RNA-seq-based transcriptome analysis, we found that LPAR5 is downregulated in the early response of HeLa cells to γ-ray irradiation. Radiation-induced alterations in LPAR5 expression were further revealed to be a bidirectional dynamic process in HeLa and A549 cells, i.e., the early downregulating phase at 2 ~ 4 h and the late upregulating phase at 24 h post-irradiation. Overexpression of LPAR5 prompts EMT programing and migration of cancer cells. Moreover, increased expression of LPAR5 is significantly associated with IR-induced EMT and confers radioresistance to cancer cells. Knockdown of LPAR5 suppressed IR-induced EMT by attenuating the activation of ERK signaling and downstream Snail, MMP1, and MMP9 expression.

Conclusions

LPAR5 is an important upstream regulator of IR-induced EMT that modulates the ERK/Snail pathway. This study provides further insights into understanding the mechanism of radiation-induced EMT and identifies promising targets for improving the effectiveness of cancer radiation therapy.
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Metadata
Title
LPAR5 confers radioresistance to cancer cells associated with EMT activation via the ERK/Snail pathway
Authors
Xiao-Ya Sun
Hao-Zheng Li
Da-Fei Xie
Shan-Shan Gao
Xin Huang
Hua Guan
Chen-Jun Bai
Ping-Kun Zhou
Publication date
01-12-2022
Publisher
BioMed Central
Keyword
Radiotherapy
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03673-4

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