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

Publisher: John Wiley & Sons Ltd Country of Publication: United States NLM ID: 101595310 Publication Model: Print Cited Medium: Internet ISSN: 2045-7634 (Electronic) Linking ISSN: 20457634 NLM ISO Abbreviation: Cancer Med Subsets: MEDLINE

Original Publication: [Malden, MA] : John Wiley & Sons Ltd., c2012-

Carcinoma, Non-Small-Cell Lung*/genetics ; Carcinoma, Non-Small-Cell Lung*/metabolism ; Carcinoma, Non-Small-Cell Lung*/pathology ; Stathmin*/genetics ; Stathmin*/metabolism ; Lung Neoplasms*/genetics ; Lung Neoplasms*/pathology ; Lung Neoplasms*/metabolism ; RNA, Circular*/genetics ; RNA, Circular*/metabolism ; Cell Proliferation* ; Gene Expression Regulation, Neoplastic* ; Disease Progression*; Humans ; Mice ; Animals ; Poly(A)-Binding Protein I/metabolism ; Poly(A)-Binding Protein I/genetics ; Cell Line, Tumor ; RNA, Messenger/metabolism ; RNA, Messenger/genetics ; Cell Movement ; Forkhead Transcription Factors/metabolism ; Forkhead Transcription Factors/genetics ; Mice, Nude ; RNA Stability ; Female ; Male

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.
(© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

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2021J245 Natural Science Foundation of Ningbo Municipality; 2021Y14 Ningbo Medical Science and Technology Plan Project; Wu Jieping Medical Foundation; 2022KY335 Medical Science and Technology Project of Zhejiang Province; 2023KY1112 Medical Science and Technology Project of Zhejiang Province; 2023RC084 Medical Science and Technology Project of Zhejiang Province; XYJH-1-CZX "Xinyu" young technical backbone training program of the First Affiliated Hospital of Ningbo University

Keywords: NSCLC; PABPC1; RNA–protein interaction; STMN1; circFOXK2

0 (Stathmin)
0 (STMN1 protein, human)
0 (RNA, Circular)
0 (Poly(A)-Binding Protein I)
0 (RNA, Messenger)
0 (Forkhead Transcription Factors)

Date Created: 20250227 Date Completed: 20250227 Latest Revision: 20250301

20250301

PMC11866311

10.1002/cam4.70729

40013670