CircLAMC1 attenuates NSCLC malignant progression through modulation of the miR-27a-3p/PAQR3/NF-κB/p53 axis

Non-small cell lung cancer, the predominant subtype of lung cancer, is associated with high mortality and poor prognosis, underscoring the need for novel therapeutic targets. CircRNAs have emerged as important regulators of tumor progression owing to their high stability and tissue-specific expression. Our previous study demonstrated that PAQR3 suppresses NSCLC progression through the NF-κB/p53 axis; however, the upstream regulatory mechanism governing PAQR3 expression remains largely unknown. Therefore, we characterized the biological function and molecular mechanism of circLAMC1 in NSCLC and explored its regulatory relationship with PAQR3. CircLAMC1 was experimentally validated as a bona fide circular RNA and was found to be predominantly localized in the cytoplasm. RT-qPCR analysis revealed that circLAMC1 was significantly downregulated in NSCLC tissues and cell lines, and lower circLAMC1 expression was significantly associated with larger tumor size and poorer differentiation. Functional studies demonstrated that circLAMC1 overexpression inhibited NSCLC cell proliferation and migration, induced S cell-cycle arrest, and promoted apoptosis both in vitro and in vivo. Mechanistically, bioinformatic analyses and dual-luciferase reporter assays verified the interactions between circLAMC1 and miR-27a-3p, as well as between miR-27a-3p and PAQR3. CircLAMC1 overexpression decreased miR-27a-3p expression and increased PAQR3 expression. Rescue experiments further demonstrated that miR-27a-3p partially abrogated the tumor-suppressive effects of circLAMC1 and PAQR3 in NSCLC cells. Moreover, circLAMC1 overexpression modulated the PAQR3/NF-κB/p53 axis in A549 cells. Collectively, our findings provide the first evidence that circLAMC1 suppresses NSCLC progression through the miR-27a-3p/PAQR3/NF-κB/p53 axis, revealing a previously unrecognized regulatory network in NSCLC and highlighting circLAMC1 as a potential therapeutic target for NSCLC.