Overexpression of ERCC6L correlates with poor prognosis and confers malignant phenotypes of lung adenocarcinoma.

Abstract

Excision repair cross-complementation group 6 like (ERCC6L) has been reported to be upregulated in a variety of malignant tumors and plays a critical oncogenic role. However, the role and molecular mechanism of ERCC6L in lung adenocarcinoma (LUAD) remain unclear, and were therefore investigated in the present study. Clinical data of patients with LUAD were obtained and bioinformatics analysis was performed to investigate the expression characteristics, prognostic value, and biological function of ERCC6L. In addition, cell function experiments were performed to detect the effect of ERCC6L silencing on the biological behavior of LUAD cells. The results revealed that ERCC6L expression was significantly higher in LUAD tissues vs. normal lung tissues and closely associated with nodal invasion, advanced clinical stage and survival in LUAD. Overexpression of ERCC6L was an independent prognostic biomarker of overall survival, progression-free interval, and disease-specific survival in patients with LUAD. DNA amplification and low methylation levels of ERCC6L suggested regulation at both the genetic and epigenetic levels. The most significant positive genes co-expressed with ERCC6L were mainly enriched in the cell cycle signaling pathway. The major functions of ERCC6L in LUAD cells were positively correlated with the cell cycle, DNA damage, DNA repair, proliferation, invasion and epithelial-mesenchymal transition (EMT). Knockdown of ERCC6L inhibited the proliferative, migratory and invasive abilities of A549 and PC9 cells. It also promoted cell apoptosis, and led to cell cycle arrest in the S phase. ERCC6L may regulate the EMT process through the Wnt/β-catenin and Wnt/Notch 3 signaling pathways, thus regulating the tumorigenesis and progression of LUAD. The overexpression of ERCC6L may be a biological indicator for the diagnosis and prognosis of LUAD. ERCC6L may be a novel molecular target for the treatment of lung cancer.