GINS1 facilitates the development of lung adenocarcinoma via Wnt/β-catenin activation.

Abstract

Background: Lung adenocarcinoma(LUAD) is the primary reason for cancer-related deaths globally. GINS1 has a significant regulatory function in DNA replication. It is overexpressed in various malignant tumors, but the specific molecular mechanisms of GINS1 in LUAD pathogenesis are not fully elucidated. This is the first report that GINS1 enhances LUAD by activating Wnt/β-catenin signaling pathway, and may serve as a potential target for therapy.

Methods: Bioinformatic analysis including analysis of difference, survival analysis and pathway enrichment, immunohistochemistry(IHC), western blotting(WB), and quantitative real time polymerase chain reaction(qRT-PCR) were used to detect GINS1 expression in LUAD cell lines and tissues. A range of in vivo and in vitro experiments, such as cck-8, EdU, cloning experiment, wound healing experiment and transwell experiment, confirmed that GINS1 facilitated the proliferation and migration of LUAD. Additionally, the potential mechanism of GINS1 was hypothesized through WB and transcriptome sequencing. The rescue experiment was used to verify our conclusion.

Results: In this study, we discovered that GINS1 is significantly overexpressed in LUAD cell lines and tissues. Analysis of Kaplan - Meier survival data indicated that high levels of GINS1 expression are often linked to unfavorable survival outcomes. Additionally, a series of experiments showed that silencing GINS1 led to less proliferation and migration of LUAD cell lines, while its overexpression enhanced tumor progression. Furthermore, subcutaneous tumor experiments in nude mice supported the role of GINS1 in promoting tumor development in vivo. Lastly, transcriptome sequencing revealed that tumor progression is related to cell cycle (G1 to S phase transition associated with cyclinD) and β-catenin signaling pathway, which we subsequently validated using WB. A series of rescue experiment further confirmed that GINS1 facilitates the advancement of LUAD via the β-catenin signaling pathway.

Conclusions: Our findings suggest that GINS1 plays a critical role in the progression of LUAD by modulating key molecular pathways, particularly the β-catenin signaling pathway., and it might serve as a potential new target of β-catenin signaling pathway for treatment of LUAD.