PAR2 Promoter Hypomethylation Regulates PAR2 Gene Expression and Promotes Lung Adenocarcinoma Cell Progression

Abstract

Objective. Protease-activated receptor-2 (PAR2) also known as F2RL1 is a G protein-coupled receptor that intimately correlates with cancer occurrence. DNA methylation turns out a vital mechanism regulating gene expression, while PAR2 promoter methylation is proven to be involved in cancer development. Hence, this study attempted to clarify the molecular mechanism by which PAR2 mediates lung adenocarcinoma (LUAD) progression, via identifying the effect of PAR2 promoter methylation on LUAD cell progression. Methods. Associations of PAR2 promoter methylation with PAR2 gene expression and prognosis of LUAD patients were analyzed via bioinformatics analysis. PAR2 promoter methylation and gene expression at the cellular level were measured using methylation-specific PCR, qRT-PCR, and Western blot assays. DNA methyltransferase inhibitor 5-AzadC was used to treat cells to assess PAR2 gene expression alteration. Cell biological behaviors upon PAR2 overexpression were characterized via MTT, wound healing assay, and Transwell assay. Results. Bioinformatics analysis revealed that PAR2 promoter methylation was negatively related to PAR2 gene expression, while PAR2 promoter hypermethylation and low gene expression indicated favorable LUAD prognosis. Besides, it turned out that PAR2 presented upregulated expression and hypomethylated promoter in LUAD cells. Moreover, PAR2 gene expression was elevated in cells treated with 5-AzadC, and the proliferative, migratory, and invasive capabilities of cells with 5-AzadC or high PAR2 gene expression were all enhanced. Conclusion. In sum, PAR2 promoter hypomethylation potentiates LUAD cell progression, in turn affecting the prognosis of LUAD patients.

Comprehensive analysis of a novel signature incorporating lipid metabolism and immune-related genes for assessing prognosis and immune landscape in lung adenocarcinoma

“…Moreover, the results of external validation based on five GEO datasets and prognostic meta-analysis all confirmed the relatively better robustness of the prognostic signature compared to previous studies (9,37). F2RL1, also known as protease-activated receptor 2 (PAR2), has been reported to be associated with the occurrence and development of lung adenocarcinoma (44) and intestinal tumors (45,46). A recent study revealed that hypomethylation of the F2RL1 promoter could upregulate its expression and promote the proliferation, migration, and invasion of LUAD cells (44).…”

“…F2RL1 , also known as protease-activated receptor 2 ( PAR2 ), has been reported to be associated with the occurrence and development of lung adenocarcinoma ( 44 ) and intestinal tumors ( 45 , 46 ). A recent study revealed that hypomethylation of the F2RL1 promoter could upregulate its expression and promote the proliferation, migration, and invasion of LUAD cells ( 44 ). The ADRB2 gene encodes the beta2-adrenergic receptor ( β 2-AR), which plays a crucial role in facilitating bronchodilation ( 47 ).…”

Development and validation of an immune-related gene prognostic index for lung adenocarcinoma

“…The CD79A (CD79a molecule) is encoded by the MB - 1 gene, and its mutation results in a complete arrest of B-cell development ( 24 ). F2R like trypsin receptor 1 (F2RL1) is a G-protein-coupled receptor ( 25 ) that is significantly upregulated in ovarian, cervical, and lung cancers, and enhances tumor cell proliferation, migration, and invasion ( 26 - 29 ). Glia maturation factor gamma (GMFG) is a 17 kDa protein, which mediates monocyte, neutrophil, and T-lymphocyte migration ( 30 - 32 ).…”