Origin recognition complex subunit 1 (ORC1) augments malignant behaviors of lung adenocarcinoma cells via targeting Wnt signaling

It has been reported that origin recognition complex subunit 1 (ORC1) plays an oncogenic role in certain human cancers. Nevertheless, its regulatory function in lung adenocarcinoma (LUAD) progression was poorly understood. In this study, gene and protein levels were measured via RT-qPCR and Western blotting. LUAD cell viability, apoptosis, and metastasis were determined via CCK-8, TUNEL, and Transwell assays. Bioinformatics analyses were performed using Genotype Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases. Herein, it was revealed that ORC1 was evidently upregulated and positively correlated to unsatisfactory prognosis in LUAD. Besides, single-sample gene set enrichment analysis (ssGSEA) revealed that ORC1 is negatively associated with 17 immune infiltrating cells and differently expressed in several kinds of immune cells. Also, Gene Ontology (GO) analysis indicated the involvement of ORC1 in several molecular functions. In addition, in vitro experiments demonstrated that ORC1 facilitated malignant behaviors of LUAD cells; moreover, animal assays further affirmed that ORC1 promoted LUAD tumor growth in vivo. As for the molecular mechanisms involved, it was found that ORC1 depletion inhibited the Wnt pathway in LUAD cells. Furthermore, rescue experiments demonstrated that Wnt signaling activation could abate the impacts of ORC1 knockdown on tumorigenic phenotypes of LUAD cells. In conclusion, our findings demonstrated that ORC1 promoted LUAD progression by regulating the Wnt signaling, indicating ORC1 could be an auspicious biomarker or target for LUAD diagnosis and treatment.

Automated summary

The study demonstrates that ORC1 is upregulated in lung adenocarcinoma (LUAD) and correlates with poor prognosis. ORC1 is negatively associated with immune infiltrating cells and involved in various molecular functions. In vitro and in vivo experiments show that ORC1 promotes malignant behaviors and tumor growth of LUAD cells. Mechanistically, ORC1 regulates the Wnt signaling pathway in LUAD cells. Therefore, ORC1 could serve as a promising biomarker or therapeutic target for LUAD.