Medical College, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region 530004, P.R. China.
Intensive Care Unit, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.
Oncol Rep. 2022 Jul;48(1). doi: 10.3892/or.2022.8342. Epub 2022 Jun 3.
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.
切除修复交叉互补基因 6 样（ERCC6L）已被报道在多种恶性肿瘤中上调，并且发挥关键的致癌作用。然而，ERCC6L 在肺腺癌（LUAD）中的作用和分子机制尚不清楚，因此本研究对此进行了探讨。本研究获取了 LUAD 患者的临床数据，并进行了生物信息学分析，以研究 ERCC6L 的表达特征、预后价值和生物学功能。此外，还进行了细胞功能实验，以检测 ERCC6L 沉默对 LUAD 细胞生物学行为的影响。结果显示，与正常肺组织相比，LUAD 组织中 ERCC6L 的表达显著升高，并且与淋巴结浸润、晚期临床分期和 LUAD 患者的生存密切相关。ERCC6L 的过表达是 LUAD 患者总生存期、无进展生存期和疾病特异性生存期的独立预后生物标志物。ERCC6L 的 DNA 扩增和低甲基化水平表明其在遗传和表观遗传水平上受到调控。与 ERCC6L 表达最显著正相关的基因主要富集在细胞周期信号通路中。ERCC6L 在 LUAD 细胞中的主要功能与细胞周期、DNA 损伤、DNA 修复、增殖、侵袭和上皮-间充质转化（EMT）呈正相关。敲低 ERCC6L 抑制了 A549 和 PC9 细胞的增殖、迁移和侵袭能力，同时促进了细胞凋亡，并导致细胞周期在 S 期停滞。ERCC6L 可能通过 Wnt/β-catenin 和 Wnt/Notch3 信号通路调节 EMT 过程，从而调节 LUAD 的发生和进展。ERCC6L 的过表达可能是 LUAD 诊断和预后的生物学指标。ERCC6L 可能是治疗肺癌的新的分子靶点。
