Mex3a interacts with LAMA2 to promote lung adenocarcinoma metastasis via PI3K/AKT pathway

Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. In this study, we found that RBP Mex3a was significantly upregulated in LUAD tissues and elevated Mex3a expression was associated with poor LUAD prognosis and metastasis. Furthermore, we demonstrated that Mex3a knockdown significantly in...

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Published in:Cell death & disease 2020-08, Vol.11 (8), p.614-614, Article 614
Main Authors: Liang, Jinghui, Li, Haixia, Han, Jingyi, Jiang, Jin, Wang, Jiang, Li, Yongmeng, Feng, Zitong, Zhao, Renchang, Sun, Zhenguo, Lv, Bin, Tian, Hui
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
Adenocarcinoma
Adenocarcinoma of Lung - genetics
Adenocarcinoma of Lung - metabolism
Adenocarcinoma of Lung - pathology
AKT protein
Animals
Cell adhesion & migration
Cell Line, Tumor
Cell migration
Cell Movement - genetics
Cell Proliferation - genetics
Extracellular matrix
Extracellular Matrix - metabolism
Female
Gene expression
Gene Expression Regulation, Neoplastic
Humans
Immunoprecipitation
Laminin
Laminin - genetics
Laminin - metabolism
Lung cancer
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Male
Metastases
Metastasis
Mice, Inbred BALB C
Middle Aged
Neoplasm Invasiveness
Neoplasm Metastasis
Phosphatidylinositol 3-Kinases - metabolism
Phosphoproteins - genetics
Phosphoproteins - metabolism
Prognosis
Protein Binding
Proto-Oncogene Proteins c-akt - metabolism
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Signal Transduction
Survival Analysis
Transcriptomes
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Summary:Lung adenocarcinoma (LUAD) is the main subtype of lung cancer. In this study, we found that RBP Mex3a was significantly upregulated in LUAD tissues and elevated Mex3a expression was associated with poor LUAD prognosis and metastasis. Furthermore, we demonstrated that Mex3a knockdown significantly inhibited LUAD cell migration and invasion in vitro and metastasis in nude mice. Transcriptome sequencing indicated that Mex3a affected gene expression linked to ECM-receptor interactions, including laminin subunit alpha 2(LAMA2). RNA immunoprecipitation (RIP) assay revealed Mex3a directly bound to LAMA2 mRNA and Mex3a increased the instability of LAMA2 mRNA in LUAD cells. Furthermore, we discovered that LAMA2 was surprisingly downregulated in LUAD and inhibited LUAD metastasis. LAMA2 knockdown partially reverse the decrease of cell migration and invasion caused by Mex3a knockdown. In addition, we found that both Mex3a and LAMA2 could influence PI3K-AKT pathway, which are downstream effectors of the ECM-receptor pathway. Moreover, the reduced activation of PI3K-AKT pathway in caused by Mex3a depletion was rescued by LAMA2 knockdown. In conclusion, we demonstrated that Mex3a downregulates LAMA2 expression to exert a prometastatic role in LUAD. Our study revealed the prognostic and prometastatic effects of Mex3a in LUAD, suggesting that Mex3a can serve as a prognostic biomarker and a target for metastatic therapy.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-020-02858-3