Molecular Mechanism of Cyclin E1 in Lung Adenocarcinoma and Their Cellular Response

Abstract

The purpose of this study was to explore the role and molecular mechanism of CCNE1 in lung adenocarcinoma (LUAD). CCNE1 expression was analyzed in LUAD tissues and cell lines by GEPIA and qRT-PCR, and its correlation with patient survival was studied using TCGA. CCNE1 overexpression was tested for its effects on cellular functions. METTL3 was predicted as a downstream gene of CCNE1 and their correlation was analyzed in lung adenocarcinoma. MeRIP was used to measure the m6A level of CCNE1 mRNA 3′-UTR after METTL3 overexpression. Dual luciferase reporter gene experiments were conducted to determine the effect of METTL3 knockdown on CCNE1 activity. Recovery experiments were performed to evaluate the CCNE1-METTL3 regulation. CCNE1 was up-regulated in LUAD cells and tissues and linked to patient prognosis. Highly expressed CCNE1 increased LUAD proliferation. METTL3 was also highly expressed in LUAD tissues and positively correlated with CCNE1 expression. METTL3 reduced CCNE1 methylation and increased expression. Additionally, METTL3 overexpression partially reversed the inhibitory effect of CCNE1 silencing on LUAD cell proliferation. This study found that CCNE1 was markedly overexpressed in lung adenocarcinoma. METTL3 can inhibit the methylation level of CCNE1. Highly expressed CCNE1 can promote the proliferation of lung adenocarcinoma.