Transcriptome analysis reveals the potential biological function of FSCN1 in HeLa cervical cancer cells

Abstract

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, ANGPTL4) 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.

N6‐methyladenosine methylation on FSCN1 mediated by METTL14/IGF2BP3 contributes to human papillomavirus type 16‐infected cervical squamous cell carcinoma

“…m6A methyltransferase METTL14 can catalyse m6A methylation modification on mRNA, while reading protein IGF2BP3 can recognize the modification and affect gene expression, thereby affecting gene expression. FSCN1 is closely related to cell motility, EMT, migration, inflammation and immunity and has been reported as a potential therapeutic target for various cancers 20–23 . Interestingly, FSCN1 was predicted to have multiple m6A modification sites on its mRNA sequence through a sequence‐based m6A modification site predictor (http://www.cuilab.cn/sramp/).…”

Identification of novel molecules and pathways associated with fascin actin‑bundling protein 1 in laryngeal squamous cell carcinoma through comprehensive transcriptome analysis

“…Finally, several studies have been conducted on the potential mechanisms through which FSCN1 affects the expression of a large number of genes ( 29 , 31 ). For example, Saad et al ( 31 ) revealed that phosphorylated FSCN1 (p-FSCN1) localized in the nucleus and regulated histone methylation and gene transcription.…”

Cross‐talk of pyroptosis‐based subtypes, the development of a risk classifier and immune responses in cervical cancer

“…22 Guo and his colleagues demonstrated that FSCN1 could be an indicator of enhanced invasive effect in CC for its positive correlation with a proangiogenic factor ANGPTL4, as revealed by the expression analysis of CC tumor tissue in TCGA. 23 The oncogenic role of Cadherin-3 (CDH3) has been well documented. In breast cancer, CDH3 overexpression mediates aggressive behavior of tumor cells, mainly associating with the exaggerated stem cell properties.…”

“…As a member of the fascin family, FSCN1 is upregulated in various tumor tissues, including CC 22 . Guo and his colleagues demonstrated that FSCN1 could be an indicator of enhanced invasive effect in CC for its positive correlation with a proangiogenic factor ANGPTL4, as revealed by the expression analysis of CC tumor tissue in TCGA 23 . The oncogenic role of Cadherin‐3 (CDH3) has been well documented.…”