Has_circ_0002360 facilitates immune evasion by enhancing heterogeneous nuclear ribonucleoprotein A1 stability, thereby promoting malignant progression in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is marked by complex molecular aberrations including differential expression of circular RNAs (circRNAs). hsa_circ_0002360, a circRNA, has been identified as overexpressed in NSCLC. This study aimed to evaluate the expression patterns of hsa_circ_0002360 and its potential role as an oncogenic factor in NSCLC. We analyzed two GEO datasets (GSE112214 and GSE158695) using R software to identify differentially expressed circRNAs. Quantitative reverse transcription PCR (qRT-PCR) assessed the expression of hsa_circ_0002360 in NSCLC tissues and cell lines compared to controls. We used siRNA and overexpression vectors to modulate hsa_circ_0002360 levels in A549 cells, followed by assays to assess proliferation, migration, invasion, apoptosis, and epithelial-mesenchymal transition (EMT). Interactions with RNA-binding proteins, specifically HNRNPA1, were investigated using RNA-pull down and RIP assays. In GEO datasets GSE112214 and GSE158695, hsa_circ_0002360 was identified as significantly overexpressed in NSCLC, a finding supported by qRT-PCR analyses showing higher levels in NSCLC tissues and cell lines compared to controls. Functional assays demonstrated that knockdown of hsa_circ_0002360 in A549 cells decreased proliferation, migration, invasion, and altered epithelial-mesenchymal transition marker expression, while inducing apoptosis, suggesting its oncogenic role. Conversely, overexpression promoted tumor characteristics, corroborated by in vivo xenograft models showing increased tumor growth. Hsa_circ_0002360's interaction with HNRNPA1, evidenced through RNA-pull down and RIP assays, implicates it in regulatory pathways that enhance NSCLC progression. This expression was also correlated with advanced TNM stages and metastasis, highlighting its potential as a therapeutic target. hsa_circ_0002360 acts as an oncogene in NSCLC, promoting tumor progression and metastasis through regulation of cell growth, apoptosis, and EMT processes. The interaction between hsa_circ_0002360 and HNRNPA1 suggests a novel mechanism of circRNA-mediated modulation of NSCLC pathology, providing potential targets for therapeutic intervention.