IGF2BP1/ORC1 Axis Influences Nonsmall Cell Lung Cancer Progression via m6A Methylation Modification

Abstract

ORC1 is a gene involved in DNA replication and is linked to various diseases. However, the role of ORC1 in cancer remains incompletely understood. The relationship between ORC1-regulated epigenetic modifications and lung cancer progression has not been systematically analyzed. Bioinformatics analysis was utilized to assess differential ORC1 expression in NSCLC and normal tissues, as well as potential m6A methylation modifiers and m6A modification sites on ORC1. Clinical samples and cell experiments validated ORC1 expression in NSCLC. RNA pulldown, MeRIP-qPCR, and mRNA stability assays analyzed the regulatory relationship between ORC1 and IGF2BP1. Cell proliferation was measured using CCK-8, while flow cytometry assessed the cell cycle and apoptosis. Western blotting evaluated the expressions of proteins related to the cell cycle, proliferation, and apoptosis. The xenograft mouse model was built by injecting human NSCLC cells, and tumor growth was monitored. After humane euthanasia, tumors were collected for weighing and staining analysis. ORC1 was upregulated in NSCLC tissues and cells, and its silencing hindered NSCLC cell proliferation. IGF2BP1 enhanced ORC1 mRNA stability through m6A modification. Both in vitro and in vivo experiments demonstrated that IGF2BP1 overexpression fostered tumor proliferation and antiapoptotic capacity, while ORC1 silencing reversed these effects, highlighting the role of the IGF2BP1/ORC1 axis in NSCLC progression. IGF2BP1 enhanced ORC1 expression by modulating its m6A methylation modification, significantly influencing NSCLC progression. This study underscored the importance of the IGF2BP1/ORC1 axis in cancer progression.