circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC.

BACKGROUND

Lung cancer has a notably high incidence and mortality rate, and understanding its occurrence and development is crucial for effective treatment. Circular RNA is closely associated with tumor progression, playing a role in tumorigenesis and development by regulating gene expression and influencing cell proliferation and apoptosis. This study aims to explore the circFOXK2 role in NSCLC occurrence and development and to elucidate its underlying mechanisms.

METHODS

qRT-PCR and Western Blot analyzed the expressions of circFOXK2, STMN1, and PABPCA in NSCLC cell lines, as well as their relationships. The roles of circFOXK2 and STMN1 in the proliferation, invasion, and migration of NSCLC cells were assessed through CCK8, EDU, and Transwell experiments. RNA pulldown assays with mass spectrometry elucidated the RNA-binding proteins of circFOXK2. Subcutaneous tumorigenesis and tail vein lung metastasis experiments analyzed the impact of circFOXK2 on tumor growth and metastasis in vivo.

RESULTS

In this study, we identified circFOXK2, which is significantly overexpressed in NSCLC, through bioinformatics screening. Elevated levels of circFOXK2 enhance the growth and metastasis of NSCLC cells. Furthermore, through experiments such as co-IP and mass spectrometry, we found that circFOXK2 interacts with PABPC1 to form a complex, which correlates positively with the progression and metastasis of tumors. Simultaneously, the circFOXK2/PABPC1 complex increases the stability of STMN1 mRNA, thereby promoting the transcription and translation of STMN1. Our experimental results indicate that the oncogenic effect of circFOXK2 requires the assistance of STMN1.

CONCLUSIONS

In summary, we have demonstrated the significant role of circFOXK2/PABPC1 in regulating STMN1 expression in NSCLC.