E2F1/MELTF 轴通过调节 Notch 信号通路促进肺腺癌的进展。
The E2F1/MELTF axis fosters the progression of lung adenocarcinoma by regulating the Notch signaling pathway.
机构信息
Department of Oncology and Hematology, The People's Hospital of Tongliang District, Chongqing 402560, China.
Department of Oncology and Hematology, The People's Hospital of Tongliang District, Chongqing 402560, China.
出版信息
Mutat Res. 2023 Jul-Dec;827:111837. doi: 10.1016/j.mrfmmm.2023.111837. Epub 2023 Sep 28.
BACKGROUND
Lung adenocarcinoma (LUAD) represents the predominant subtype of lung cancer. MELTF, an oncogene, exhibits high expression in various cancer tissues. Nevertheless, the precise role of MELTF in the progression of LUAD remains enigmatic. This work was devised to investigate the effect of MELTF on LUAD progression and its underlying mechanism.
METHODS
mRNA expression data of LUAD were from The Cancer Genome Atlas database, and the enrichment pathway of MELTF was analyzed. The upstream transcription factors of MELTF were predicted, and the correlation between MELTF and E2F1 as well as the expression of the two in LUAD tissues were dissected by bioinformatics. The expression of MELTF and E2F1 in LUAD tissues and cells was assayed by qRT-PCR. Effects of MELTF/E2F1 on proliferation, migration, and invasion of LUAD cells were tested by CCK-8, colony formation, and Transwell assays. The binding relationship between E2F1 and MELTF was estimated by dual-luciferase reporter gene assay and ChIP assay. Western blot was utilized to assay the expression of Notch signaling pathway-related proteins in different treatment groups.
RESULTS
Bioinformatics analysis and qRT-PCR results exhibited high expression of E2F1 and MELTF in LUAD tissues and cells, respectively. Dual-luciferase reporter gene assay and ChIP assay ascertained the binding of E2F1 to MELTF. MELTF was ascertained to enrich the Notch signaling pathway by bioinformatics means. In cell experiments, MELTF was shown to foster the malignant progression of LUAD cells and promoted the expression of NOTCH1 and HES1 proteins, but RO4929097 offset the effect of MELTF on cells. Rescue assay confirmed that E2F1 activated MELTF to promote LUAD progression via the Notch signaling pathway.
CONCLUSION
Together, our outcomes demonstrated that E2F1 fostered LUAD progression by activating MELTF via the Notch signaling activity. Hence, MELTF emerged as a feasible target for treating LUAD.
背景
肺腺癌（LUAD）是肺癌的主要亚型。癌基因 MELTF 在各种癌症组织中高表达。然而，MELTF 在 LUAD 进展中的确切作用仍然是个谜。本研究旨在探讨 MELTF 对 LUAD 进展的影响及其潜在机制。
方法
从癌症基因组图谱数据库中获取 LUAD 的 mRNA 表达数据，并分析 MELTF 的富集途径。预测 MELTF 的上游转录因子，并通过生物信息学方法分析 MELTF 与 E2F1 之间的相关性以及两者在 LUAD 组织中的表达情况。通过 qRT-PCR 检测 LUAD 组织和细胞中 MELTF 和 E2F1 的表达。通过 CCK-8、集落形成和 Transwell 测定评估 MELTF/E2F1 对 LUAD 细胞增殖、迁移和侵袭的影响。通过双荧光素酶报告基因检测和 ChIP 检测评估 E2F1 与 MELTF 之间的结合关系。通过 Western blot 检测不同处理组 Notch 信号通路相关蛋白的表达。
结果
生物信息学分析和 qRT-PCR 结果显示，E2F1 和 MELTF 在 LUAD 组织和细胞中的表达均较高。双荧光素酶报告基因检测和 ChIP 检测证实了 E2F1 与 MELTF 的结合。通过生物信息学方法证实 MELTF 可富集 Notch 信号通路。在细胞实验中，MELTF 促进 LUAD 细胞的恶性进展，并促进 NOTCH1 和 HES1 蛋白的表达，但 RO4929097 抵消了 MELTF 对细胞的作用。挽救实验证实，E2F1 通过 Notch 信号通路激活 MELTF 促进 LUAD 进展。
结论
综上所述，我们的研究结果表明，E2F1 通过 Notch 信号活性激活 MELTF 促进 LUAD 进展。因此，MELTF 可能成为治疗 LUAD 的可行靶点。
Zotero 插件