Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing the transcription and splicing of tumorigenesis-related genes

• Published in: PeerJ (San Francisco, CA) CA), 2023-12, Vol.11, p.e16526-e16526, Article e16526
• Main Authors: Sun, Qingchao, Liu, Ruixue, Zhang, Haiping, Zong, Liang, Jing, Xiaoliang, Ma, Long, Li, Jie, Zhang, Liwei
• Format: Article
• Language: English
• Subjects: Actin; Alternative splicing; Analysis; Antibodies; Apoptosis; Cancer; Cell proliferation; China; Ethylenediaminetetraacetic acid; FSCN1; Gene expression; Gene set enrichment analysis; Gene silencing; Genes; Genetic aspects; Genetic engineering; Genetic transcription; Health aspects; Immunoprecipitation; Life sciences; Lung cancer; Lung cancer, Non-small cell; Massachusetts; Messenger RNA; Mortality; Muscle proteins; Non-small cell lung carcinoma; NSCLC; Phenotypes; Prognosis; Protein binding; Proteins; Reagents; RNA-binding protein; Small cell lung carcinoma; Therapeutic targets; Transcription; Transcriptomes; Tumorigenesis; Tumors
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.16526

High mortality rates are prevalent among patients with non-small-cell lung cancer (NSCLC), and effective therapeutic targets are key prognostic factors. Fascin actin-bundling protein 1 (FSCN1) promotes NSCLC; however, its role as an RNA-binding protein in NSCLC remains unexplored. Therefore, we aimed to explore FSCN1 expression and function in A549 cells. We screened for alternative-splicing events and differentially expressed genes (DEGs) after silence RNA-sequencing (RNA-seq). FSCN1 immunoprecipitation followed by RNA-seq were used to identify target genes whose mRNA expression and pre-mRNA alternative-splicing levels might be influenced by FSCN1. Silencing in A549 cells affected malignant phenotypes; it inhibited proliferation, migration, and invasion, and promoted apoptosis. RNA-seq analysis revealed 2,851 DEGs and 3,057 alternatively spliced genes. Gene ontology-based functional enrichment analysis showed that downregulated DEGs and alternatively splicing genes were enriched for the cell-cycle. FSCN1 promoted the alternative splicing of cell-cycle-related mRNAs involved in tumorigenesis ( , , , , , , and ). Combined analysis of FSCN1 RNA-binding targets and RNA-seq data suggested that FSCN1 might affect , , and expression by modulating the pre-mRNA alternative-splicing levels of , , and , that were bound to long non-coding RNA transcripts ( , , , and ), which were highly abundant. Overall, extensive transcriptome analysis of gene alternative splicing and expression levels was performed in cells transfected with FSCN1 short-interfering RNA. Our data provide global insights into the regulatory mechanisms associated with the roles of FSCN1 and its target genes in lung cancer.