Circular RNA hsa_circ_0050386 suppresses non-small cell lung cancer progression via regulating the SRSF3/FN1 axis

Journal of Translational Medicine
Jinbin Chen1, Boqi Rao1, Zikun Huang1, Chen Xie1, Yang Yu1, Binyao Yang2, Di Wu3, Dedong Wang3, Fuman Qiu1, Yifeng Zhou4, Yibin Deng5, Jiachun Lü6
1The State Key Lab of Respiratory Disease, The School of Public Health, Guangzhou Medical University, Guangzhou, 511436, China
2Department of Central Laboratory, The 5th Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510700, China
3Guangzhou Center for Disease Control and Prevention, Guangzhou 510440, China
4Department of Genetics, Medical College of Soochow University, Suzhou, 215123, China
5Centre for Medical Laboratory Science, the Affiliated Hospital of Youjiang Medical University for Nationalities, No. 18 Zhongshaner Rd., Youjiang District, Baise, 533000, China
6The State Key Lab of Respiratory Disease, The First Affiliated Hospital, The School of Public Health, Guangzhou Medical University, Xinzao Town, Panyu District, Guangzhou, 511436, China

Tóm tắt

Abstract Background Lung cancer is the most prevalent cancer worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of all cases. Circular RNAs(circRNA) play crucial roles in regulating the progression of lung cancer. Despite the identification of a large number of circRNAs, their expression patterns, functions, and mechanisms of action in NSCLC development remain unclear.This study aims to investigate the transcriptional expressions, functions, and potential mechanisms of circRNA hsa_circ_0050386 in NSCLC. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized for the analysis of hsa_circ_0050386 expression. Cell proliferation was detected using the IncuCyte Live Cell Analysis System and clone formation assays. Migration and invasion of NSCLC cells were evaluated through Transwell assays. Flow cytometry was performed to assay cell cycle and apoptosis. Western blot was used to investigate protein expression. Protein binding analysis was conducted by employing pull-down assays, RNA immunoprecipitation (RIP), and mass spectrometry. The role of hsa_circ_0050386 in vivo was evaluated through the use of a xenograft model. Results The study discovered that hsa_circ_0050386 displayed lower expression levels in NSCLC tissues when compared to adjacent normal tissues. Patients exhibiting lower levels of hsa_circ_0050386 expression exhibited an inverse correlation with the Clinical Stage, T-stage, and M-stage of NSCLC. Functionally, hsa_circ_0050386 suppressed the proliferation and invasion of NSCLC cells both in vitro and in vivo. A comprehensive examination exposed the interaction between hsa_circ_0050386 and RNA binding protein Serine and arginine-rich splicing factor 3 (SRSF3), resulting in the down-regulation of Fibronectin 1 (FN1) expression, which inhibits the progression of NSCLC. Conclusions Our study shows that hsa_circ_0050386 suppresses the malignant biological behavior of NSCLC cells by down-regulating the expression of FN1, and may serve as a potential biomarker and therapeutic target for NSCLC treatment.

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Journal of Translational Medicine

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