Guo Fengqin, Liu Yanliang, Cheng Yanxiang, Zhang Qifan, Quan Weili, Wei Yaxun, Hong Li
Department of Obstetrics & Gynecology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
PeerJ. 2022 Feb 2;10:e12909. doi: 10.7717/peerj.12909. eCollection 2022.
Fascin actin-bundling protein 1 (FSCN1), an actin-bundling protein associated with cell migration and invasion, is highly expressed in various tumor tissues. FSCN1 has also been reported to be a marker of increased invasive potential in cervical cancers. However, the functions of FSCN1 are still not fully understood in cervical cancers. Here, the gene expression profile of HeLa cells transfected with FSCN1 shRNA (shFSCN1) was compared with that of cells transfected with empty vector (shCtrl). The results showed that shFSCN1 extensively affected the transcription level of 5,043 genes in HeLa cells. In particular, Gene Ontology (GO) analysis showed that a large number of upregulated genes were annotated with terms including transcription regulation and DNA binding. The downregulated genes were enriched in some cancer pathways, including angiogenesis and cell adhesion. qPCR validation confirmed that FSCN1 knockdown significantly affected the expression of selected genes in HeLa cells either negatively or positively. Expression analysis in TCGA (The Cancer Genome Atlas) revealed that FSCN1 had negative correlations with several transcription factors and a positive correlation with an angiogenic factor (angiopoietin like 4, ) in cervical tumor tissue. In particular, validation by Western blotting showed that FSCN1 knockdown decreased the protein level of ANGPTL4. Our results demonstrated that FSCN1 is not only an actin-binding protein but also a transcriptional regulator and an angiogenic factor in cervical cancer. Thus, our study provides important insights for further study on the regulatory mechanism of FSCN1 in cervical cancer.
Fascin肌动蛋白捆绑蛋白1（FSCN1）是一种与细胞迁移和侵袭相关的肌动蛋白捆绑蛋白，在各种肿瘤组织中高表达。据报道，FSCN1也是宫颈癌侵袭潜能增加的一个标志物。然而，FSCN1在宫颈癌中的功能仍未完全明确。在此，将转染FSCN1短发夹RNA（shFSCN1）的HeLa细胞的基因表达谱与转染空载体（shCtrl）的细胞的基因表达谱进行比较。结果显示，shFSCN1广泛影响HeLa细胞中5043个基因的转录水平。特别是，基因本体论（GO）分析表明，大量上调基因被注释为包括转录调控和DNA结合等术语。下调基因在一些癌症通路中富集，包括血管生成和细胞黏附。定量PCR验证证实，FSCN1敲低显著影响HeLa细胞中所选基因的表达，既有负向影响也有正向影响。癌症基因组图谱（TCGA）中的表达分析显示，在宫颈肿瘤组织中，FSCN1与几种转录因子呈负相关，与一种血管生成因子（血管生成素样4）呈正相关。特别是，蛋白质印迹法验证表明，FSCN1敲低降低了ANGPTL4的蛋白水平。我们的结果表明，FSCN1不仅是一种肌动蛋白结合蛋白，也是宫颈癌中的一种转录调节因子和血管生成因子。因此，我们的研究为进一步研究FSCN1在宫颈癌中的调控机制提供了重要见解。
