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

ABSTRACT 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 expressi...

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Main Authors: Wei Chen, Weijun Zhao, Xianqiao Wu, Tianzheng Fang, Ziyuan Chen, Zixuan Chen, Wenmin Su, Xiaodong Zhao, Yuanyuan Hu, Yiping Xu, Shuai Fang, Chengwei Zhou
Format: Article
Language:English
Published: Wiley 2025-03-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70729
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author Wei Chen
Weijun Zhao
Xianqiao Wu
Tianzheng Fang
Ziyuan Chen
Zixuan Chen
Wenmin Su
Xiaodong Zhao
Yuanyuan Hu
Yiping Xu
Shuai Fang
Chengwei Zhou
author_facet Wei Chen
Weijun Zhao
Xianqiao Wu
Tianzheng Fang
Ziyuan Chen
Zixuan Chen
Wenmin Su
Xiaodong Zhao
Yuanyuan Hu
Yiping Xu
Shuai Fang
Chengwei Zhou
author_sort Wei Chen
collection DOAJ
description ABSTRACT 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.
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spelling doaj-art-1bfe0b2cef884cde8914fe07b5eeeb5e2025-08-20T02:05:21ZengWileyCancer Medicine2045-76342025-03-01145n/an/a10.1002/cam4.70729circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLCWei Chen0Weijun Zhao1Xianqiao Wu2Tianzheng Fang3Ziyuan Chen4Zixuan Chen5Wenmin Su6Xiaodong Zhao7Yuanyuan Hu8Yiping Xu9Shuai Fang10Chengwei Zhou11Thoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaThoracic Surgery Department The First Affiliated Hospital of Ningbo University Ningbo Zhejiang People's Republic of ChinaABSTRACT 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.https://doi.org/10.1002/cam4.70729circFOXK2NSCLCPABPC1RNA–protein interactionSTMN1
spellingShingle Wei Chen
Weijun Zhao
Xianqiao Wu
Tianzheng Fang
Ziyuan Chen
Zixuan Chen
Wenmin Su
Xiaodong Zhao
Yuanyuan Hu
Yiping Xu
Shuai Fang
Chengwei Zhou
circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC
Cancer Medicine
circFOXK2
NSCLC
PABPC1
RNA–protein interaction
STMN1
title circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC
title_full circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC
title_fullStr circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC
title_full_unstemmed circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC
title_short circFOXK2 Stabilizes STMN1 mRNA via PABPC1 to Promote the Progression of NSCLC
title_sort circfoxk2 stabilizes stmn1 mrna via pabpc1 to promote the progression of nsclc
topic circFOXK2
NSCLC
PABPC1
RNA–protein interaction
STMN1
url https://doi.org/10.1002/cam4.70729
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