Hypermethylation in the promoter region inhibits LRRN3 expression and promotes proliferation of non-small cell lung cancer

Abstract

Objective To study the role of leucine rich repeat neuronal 3 (LRRN3) in the proliferation of non-small cell lung cancer and its possible mechanism of expression regulation. Methods The expression of LRRN3 in non-small cell lung cancer was detected by real-time quantitative polymerase chain reaction (qPCR), immunohistochemistry and bioinformatics retrieval; A lung cancer cell line A549-LRRN3 with stable over-expression of LRRN3 was established by lentivirus over-expression technology; The effect of LRRN3 on the proliferation of non-small cell lung cancer was detected by methyl thiazolyl tetrazolium (MTT) assay; Bioinformatics search for changes in methylation of LRRN3 promoter region and treatment of lung cancer cells by methyltransferase inhibitors to detect the effect of methylation on the regulation of LRRN3 expression; Finally, bioinformatics search analyzes the correlation between LRRN3 and lung cancer prognosis. Results The mRNA expression of LRRN3 in clinical tissues of non-small cell lung cancer (n=12) was significantly lower than that of adjacent normal tissues (n=12) (P=0.0014). The results of immunohistochemistry showed that the protein expression level of LRRN3 in non-small cell lung adenocarcinoma was lower than that in normal tissues (P=0.001), and the expression in non-small cell lung squamous cell carcinoma was also lower than that in normal tissues (P=0.003). Overexpression of LRRN3 inhibited the proliferation of tumor cells (P<0.01), and the hypermethylation of LRRN3 in the promoter region inhibited its transcriptional expression. LRRN3 was positively correlated with the survival prognosis of lung adenocarcinoma (P=5.2e-09; HR=0.48). Conclusions Hypermethylation in the promoter region of LRRN3 inhibits its transcriptional expression, thereby promoting the proliferation of lung cancer cells. Key words: Nerve tissue proteins; Carcinoma, non-small-cell lung; Methylation; Cell proliferation; Computational biology