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Published on: June 26, 2019
AGTR1 Inhibits the Progression of Lung Adenocarcinoma
Lecai Xiong1, Yanhong Wei2, Xiao Zhou1
1Department of Thoracic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China.
Purpose:
The occurrence and development of lung adenocarcinoma (LUAD) are related to many factors. Multiple researches showed that the renin-angiotensin system (RAS) plays an important role in lung cancer. This research mainly focuses on angiotensin II receptor 1 (AT1R) encoding gene AGTR1, an important part of the RAS.
Methods:
We comprehensively evaluated the expression of AGTR1 in pan-cancer based on RNA sequencing data obtained from The Cancer Genome Atlas (TCGA). We explored the correlation of AGTR1 with clinicopathological features, prognosis and tumor microenvironment in LUAD. We also explored the mechanism through enrichment analysis and verified it with cell lines and tissue samples.
Results:
We found that AGTR1 was less expressed in most tumors and related to prognosis based on the TCGA database. To further explore its mechanism, we mainly focused on LUAD. Combined with the verification results in the GEO database, AGTR1 was associated with a better prognosis in LUAD. High expression of AGTR1 was associated with less lymph node metastasis (P=0.007) and MET mutation (P=0.019). High expression of AGTR1 was related to the anti-tumor immune microenvironment with high infiltration of B cells, myeloid dendritic cells, monocytes, and low infiltration of myeloid-derived suppressor cells (all P<0.05). Enrichment analysis and in vitro verification results showed that AGTR1 was likely to play a role in LUAD through the PI3K/AKT3 pathway. Finally, we verified the above results through tissue samples and the construction of AGTR1 overexpressing cells.
Conclusion:
AGTR1 inhibits the progression of lung adenocarcinoma through the PI3K/AKT3 pathway.
Insights
The angiotensin II receptor 1 (AT1R) gene, AGTR1, inhibits lung adenocarcinoma (LUAD) progression. High AGTR1 expression correlates with better prognosis and an anti-tumor immune microenvironment, acting via the PI3K/AKT3 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Lung adenocarcinoma (LUAD) development is multifactorial.
- The renin-angiotensin system (RAS) is implicated in lung cancer.
- The angiotensin II receptor 1 (AT1R) gene, AGTR1, is a key RAS component.
Purpose of the Study:
- To investigate the role of AGTR1 in pan-cancer, with a focus on LUAD.
- To explore the association of AGTR1 with clinicopathological features, prognosis, and the tumor microenvironment in LUAD.
- To elucidate the underlying mechanism of AGTR1 action in LUAD.
Main Methods:
- Comprehensive analysis of AGTR1 expression in The Cancer Genome Atlas (TCGA) pan-cancer dataset.
- Correlation analysis of AGTR1 with LUAD clinicopathological features, prognosis, and immune cell infiltration using TCGA and GEO databases.
- Functional mechanism exploration via enrichment analysis and in vitro/tissue sample validation.
Main Results:
- AGTR1 expression is reduced in most cancers and linked to prognosis.
- In LUAD, high AGTR1 expression is associated with better prognosis, reduced lymph node metastasis, and MET mutation.
- High AGTR1 expression correlates with an anti-tumor immune microenvironment (increased B cells, dendritic cells, monocytes; decreased MDSCs) and involves the PI3K/AKT3 pathway.
Conclusions:
- AGTR1 acts as a tumor suppressor in LUAD.
- AGTR1 inhibits LUAD progression, potentially through the PI3K/AKT3 signaling pathway.
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