Hsa_circ_0081111 promotes the proliferation and metastasis of non-small cell lung cancer by regulating IGF2BP2-mediated stability of Slug mRNA

Abstract

Previous researches have indicated the oncogenic effect of circCOL1A2 in several cancers, such as tongue squamous cell carcinoma, gastric cancer, and colorectal cancer. Regrettably, the functions and mechanisms of circCOL1A2 in lung cancer, a disease with the highest global incidence and mortality rates and with 85 % of cases classified as non-small cell lung cancer (NSCLC), remain largely unexplored. Hsa_circ_0081111 (circCOL1A2) was identified from GSE236879 dataset of Gene Expression Omnibus (GEO) database. Its expression was validated in 37 paired samples of cancerous and adjacent normal tissues from NSCLC patients, as well as in cell lines. The function of hsa_circ_0081111 was analyzed using CCK-8, Matrigel transwell, Western blot, and immunofluorescence assays in vitro, and by conducting subcutaneous xenograft experiments in mouse. The underlying mechanisms were explored using bioinformatics analysis, RNA pull-down experiments, and RNA immunoprecipitation. High expression of hsa_circ_0081111 was observed in NSCLC tissues and cell lines. This was positively correlated with the TNM stage and lymph node metastasis of NSCLC patients. Hsa_circ_0081111 overexpression promoted the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells. Conversely, its downregulation showed the opposite effects. In vivo studies revealed that silencing hsa_circ_0081111 inhibited tumor growth, EMT, and MMP9 expression in tumor tissues. Mechanically, hsa_circ_0081111 enhanced Slug mRNA stability by interacting with the RNA-binding protein IGF2BP2. Taken together, hsa_circ_0081111 is an oncogenic circRNA that promotes NSCLC malignancy by regulating IGF2BP2-mediated Slug mRNA stability. Hsa_circ_0081111 has the potential to be a diagnostic and therapeutic target for NSCLC.