Hypomethylation-Mediated AGR2 Overexpression Facilitates Cell Proliferation, Migration, and Invasion of Lung Adenocarcinoma

Abstract

Objective Studies have indicated that AGR2 is crucial in many cancers. However, its methylation level in lung adenocarcinoma (LUAD) is rarely known. Hence, the effect of AGR2 methylation on LUAD was explored in the study. Methods qRT-PCR was adopted to detect the expression of AGR2 in LUAD cells and normal lung cells. Methylation-specific PCR (MSP) was used to detect the methylation of AGR2 promoter region in different cell lines. MTT, Transwell and wound healing assays were used to verify the progression of cells in each transfection group. Results The expression of AGR2 was significantly up-regulated in LUAD cells relative to that in normal cells. Moreover, the expression of AGR2 was inversely modulated by DNA methylation, and the hypomethylation of CpG islands would lead to the increased expression of AGR2. Finally, overexpression and hypomethylation of AGR2 facilitated the proliferation, invasion and migration of LUAD cells. Conclusion These results demonstrated that hypomethylation of AGR2 promoter region promoted the expression of AGR2 in LUAD cells, thus promoting the progression of LUAD cells.

Single‐cell transcriptomic analysis uncovers intratumoral heterogeneity and drug‐tolerant persister in ALK‐rearranged lung adenocarcinoma

“…CCL20 has been shown to play a role in modulating the tumor immune microenvironment [ 5 ]. In alectinib‐resistant tumor organoids of TS485T‐O, besides the activated IL‐17 pathway, upregulation of ribosomal protein L10 ( RPL10 ), nicotinamide phosphoribosyltransferase ( NAMPT ) and anterior gradient‐2 ( AGR2 ) were observed (Figure 1F ), and the functions of these genes in lung cancer were mentioned in previous studies [ 6 , 7 ]. In contrast, we found that the actin cytoskeleton regulatory pathway was downregulated in both FA34‐O crizotinib‐resistant and alectinib‐resistant tumor organoids ( Supplementary Figure S2E‐F ).…”

Epigenetic Alterations of DNA Methylation and miRNA Contribution to Lung Adenocarcinoma

“…CpG island-specific methylation in the promoter region of genes is associated with gene silencing ( Morgan et al, 2018 ), which changes the expression of downstream hub genes and promotes abnormal cell proliferation ( Kulis and Esteller, 2010 ). DNA methylation and miRNA expression can make a real difference in LUAD by up- or downregulating gene expressions ( Herbst et al, 2018 ; He et al, 2021 ). Aberrant DNA methylation and miRNA expression can be regarded as impactful biomarkers to distinguish LUAD from normal samples ( Ren et al, 2019 ; Sherafatian and Arjmand, 2019 ), which would be helpful in diagnosis, assessment of treatment, and prediction of prognosis ( Ye et al, 2021 ).…”

Current data and future perspectives on DNA methylation in ovarian cancer (Review)

“…AGR2, a protein disulfide isomerase localized to the endoplasmic reticulum or secreted into the extracellular space, has been linked to cancer progression in patients with similar tumors (112)(113)(114). According to the study by Sung et al (115), which used a mouse model of human OC metastasis, the CpG site in the promoter region of AGR2 is hypermethylated in metastatic tumor tissue, which typically results in AGR2 overexpression.…”