Hypermethylation in the promoter region inhibits LRRN3 expression and promotes proliferation of non-small cell lung cancer / 中国医师杂志

ABSTRACT

Objective To study the role of leucine rich repeat neuronal 3 (LRRN3) in the prolif-eration 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 LR-RN3 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 adenocar-cinoma was lower than that in normal tissues (P=0. 001), and the expression in non-small cell lung squa-mous cell carcinoma was also lower than that in normal tissues (P=0. 003). Overexpression of LRRN3 in-hibited the proliferation of tumor cells (P<0. 01), and the hypermethylation of LRRN3 in the promoter re-gion 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.