The Polymorphism and Expression of EGFL7 and miR-126 Are Associated With NSCLC Susceptibility

Abstract

Previous investigations have reported that microRNA-126 (miR-126) and its host gene, epidermal growth factor-like domain-containing protein 7 (EGFL7) are involved in lung cancer progression, suggesting EGFL7 and miR-126 play a joint role in lung cancer development. In this study, we analyzed the methylation-associated regulation of EGFL7 and miR-126 in non-small cell lung cancer (NSCLC) and further investigated the association between EGFL7/miR-126 polymorphisms and NSCLC susceptibility in the Han Chinese population. Based on our data, relative to those in adjacent normal tissue, both EGFL7 expression and miR-126 expression were decreased significantly in lung cancer tissue (P = 3x10-4 and P < 1x10-4), and the expression of EGFL7 mRNA and miR-126 was significantly correlated in both NSCLC tissue n = 46, r = 0.43, P = 0.003 and adjacent normal tissue n = 46, r = 0.37, P = 0.011. Differential methylation analysis indicated that methylation levels of multiple CG loci in EGFL7 were significantly higher in the lung cancer samples than in the normal samples (P < 0.01). Moreover, EGFL7 mRNA and miR-126 were significantly upregulated after treatment with the DNA demethylating agent 5-aza-2′-deoxycytidine (5-Aza-CdR) in lung cancer cell lines. In addition, the A allele of rs2297538 was significantly associated with a decreased NSCLC risk (OR = 0.68, 95% CI: 0.52~0.88), and the expression of EGFL7 and miR-126 was significantly lower in rs2297538 homozygous G/G tumor tissue than in A/G+A/A tumor tissue (P = 0.01 and P = 0.002). Our findings suggest that the expression of EGFL7 and miR-126 in NSCLC can be concomitantly downregulated through methylation and the EGFL7/miR-126 polymorphism rs2297538 is correlated with NSCLC risk. Together, these results provide new insights into the pathogenesis of NSCLC.

Cuproptosis-Related Gene – SLC31A1, FDX1 and ATP7B – Polymorphisms are Associated with Risk of Lung Cancer

“… 42 Liu et al have found that EGFL7/miR-126 polymorphism rs2297538 was associated with the risk of non-small cell lung cancer. 43 In addition, Yu et al have identified a novel regQTL-SNP, rs3768617, may have effects on lung cancer risk by influencing the expression of miRNA-548b-3p and LAMC1. 44 These studies remind us that we could also explore the association between SNPs in cuproptosis-related lncRNA, miRNA and lung cancer risk, and might identify some novel regQTL-SNP related to lung cancer risk in further studies.…”

The Role of the Selected miRNAs as Diagnostic, Predictive and Prognostic Markers in Non-Small-Cell Lung Cancer

“…It has been established that it could serve as a diagnostic factor due to a significant decrease in its expression in advanced-stage NSCLC compared to the early-stage NSCLC cases [ 41 ]. It was found to be strongly downregulated in the NSCLC [ 40 ] cell lines [ 27 , 75 , 76 ], tissues [ 27 , 74 , 75 , 76 ], body fluids [ 74 ], and serum-derived exosomes [ 73 ]. An increase in its expression supresses the aggressiveness of the tumour cells through various pathways [ 27 , 40 , 74 , 75 , 77 ].…”

Role of EGFL7 in human cancers: A review

“…The expression of miR‐126 and EGFL7 in NSCLC can be concomitantly downregulated through methylation of CpG islands, thereby inhibiting NSCLC cell proliferation and tumor growth. A recent study observed that EGFL7 and miR‐126 are associated with the risk of NSCLC in the Han Chinese population (Liu et al, 2022).…”