CircFNIP1 Regulates Proliferation and Invasion in Lung Cancer Cells and Represents a Potential Therapeutic Target.

Background: Lung cancer (LC) remains the leading cause of cancer-related mortality. Circular RNAs (circRNAs) are emerging as important regulators in cancer biology. Objectives: This study investigated the functional role and therapeutic potential of circFNIP1 (hsa_circ_0073858) in LC. Materials and Methods: The expression of circFNIP1 in multiple lung cancer cell lines was quantified using quantitative real-time PCR, and its subcellular localization was determined by fluorescence in situ hybridization. To investigate function, circFNIP1 was silenced in PC-9 and SPC-A1 cells using siRNA-mediated knockdown. Cellular proliferation was measured by CCK-8 and colony formation assays, while apoptosis was evaluated via flow cytometry. Cell migration and invasion capacities were assessed using wound healing and transwell assays. In vivo tumorigenic potential was examined by establishing subcutaneous xenografts in nude mice, followed by intratumoral administration of antisense oligonucleotides targeting circFNIP1. Bioinformatics analyses, including interrogation of circRNA and miRNA databases and protein-protein interaction networks, were performed to predict circFNIP1-associated miRNAs and downstream targets. All experiments were conducted in triplicate, and statistical analyses were performed to determine significance. Results: CircFNIP1 was highly expressed in LC cells and localized to both the nucleus and cytoplasm. Knockdown of circFNIP1 significantly reduced proliferation, colony formation, migration, and invasion in vitro, and suppressed tumor growth in a mouse xenograft model. Bioinformatics predicted miR-1231 and miR-657 as key targets, with ICAM1 identified as a downstream effector of miR-657. Conclusions: CircFNIP1 functions as an oncogenic circRNA in LC and represents a promising target for RNA-based therapeutic strategies. These findings provide a basis for the development of circFNIP1-targeted interventions in LC management.