Circular RNA circLAMC1 suppresses the malignant progression of non-small cell lung cancer through a newly identified regulatory pathway, according to laboratory findings published in Biology Direct. Non-small cell lung cancer represents the predominant subtype of lung cancer and remains linked to high mortality rates and poor clinical prognosis. Circular RNAs have emerged as key regulators of tumor progression owing to their high stability and tissue-specific expression patterns, leading investigators to characterize how circLAMC1 functions within lung cancer cells and how it influences downstream tumor-suppressive signaling.

Experimental testing confirmed that circLAMC1 is an authentic circular RNA that is predominantly localized within the cytoplasm. Quantitative reverse transcription PCR analysis revealed that circLAMC1 expression was significantly downregulated across non-small cell lung cancer tissues and cultured cell lines compared to control samples. Furthermore, clinical sample evaluations demonstrated that reduced circLAMC1 expression was significantly associated with larger tumor dimensions and poorer histological tumor differentiation.

Functional experiments demonstrated that circLAMC1 plays a direct role in limiting cancer cell growth and spread in both laboratory cultures and animal models. Overexpressing circLAMC1 significantly inhibited non-small cell lung cancer cell proliferation and cell migration. The intervention also induced cell-cycle arrest specifically at the S phase and promoted cellular apoptosis both in vitro and in vivo, demonstrating clear tumor-suppressive activity in these experimental systems.

Mechanistic assays clarified how circLAMC1 mediates its protective molecular effects against lung tumor progression. Bioinformatic evaluations and dual-luciferase reporter assays confirmed direct molecular interactions between circLAMC1 and the microRNA miR-27a-3p. The same experimental approach verified binding between miR-27a-3p and PAQR3, establishing a competitive regulatory network between these RNA molecules.

Subsequent laboratory tests confirmed that elevating circLAMC1 decreased miR-27a-3p levels while increasing the expression of PAQR3. Previous research had shown that PAQR3 suppresses non-small cell lung cancer progression, although its upstream regulatory control remained largely unknown. Rescue assays showed that introducing miR-27a-3p partially abrogated the tumor-suppressive actions of circLAMC1 and PAQR3 in non-small cell lung cancer cells, confirming that circLAMC1 operates by modulating this intermediary microRNA.

At the signaling level, overexpressing circLAMC1 successfully modulated the downstream PAQR3/NF-κB/p53 pathway in A549 lung cancer cells. The authors concluded that their findings provide the first direct evidence that circLAMC1 curbs non-small cell lung cancer progression via the miR-27a-3p/PAQR3/NF-κB/p53 axis, pointing to circLAMC1 as an exploratory therapeutic target while emphasizing that these findings reflect preclinical cellular and animal models rather than immediate clinical applications.

Subject of Research: Preclinical study on circLAMC1 regulation of non-small cell lung cancer progression

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

Article References: Long, K., Tang, Y., Duan, S., Gao, M., Xu, G., Song, Y., & Ke, X. (2026). CircLAMC1 attenuates NSCLC malignant progression through modulation of the miR-27a-3p/PAQR3/NF-κB/p53 axis. Biology Direct. https://doi.org/10.1186/s13062-026-00999-7

Image Credits: AI Generated

DOI: 10.1186/s13062-026-00999-7

Keywords: circLAMC1, circular RNA, non-small cell lung cancer, NSCLC, miR-27a-3p, PAQR3, NF-κB, p53, A549 cells, tumor progression, cell proliferation, cell migration, S cell-cycle arrest, apoptosis, dual-luciferase reporter assay, RT-qPCR, tumor differentiation, tumor size