Filamin B extensively regulates the transcription and alternative splicing and is associated with apoptosis in HeLa cells

ABSTRACT: Post-transcriptional mechanisms is an important means for the body to fight against cancer, and it may also be hijacked by tumor cells to help them adapt to local microenvironment. Filamin B (FLNB), an actin-binding protein and providing crucial scaffolds for cell motility and signaling, was also identified as one of RNA binding proteins (RBPs). Recent works showed that FLNB might play important role not only in skeletal development but also in the regulation of tumorigenesis. However, the effects of dysregulated expression of FLNB at a molecular level are unclear. In this study, we used RNA-seq to analyze the global transcriptional level changes and alternative splicing between the knocked-down FLNB and the control in Hela cells. Reduced levels of FLNB led to a significant decrease in cell apoptosis, compared with control cells. FLNB knockdown extensively regulated the expression of genes in cell apoptosis, tumorigenesis, metastases, transmembrane transport, cartilage and nerve development. Moreover, FLNB regulated alternative splicing of a large number of genes enriched in cell death and apoptotic process. Meanwhile, some genes and alternative splicing related to skeletal development were enriched and regulated by FLNB. Quantitative RT-PCR confirmed the FLNB-regulated transcription and alternative splicing. This study provides the first transcriptome-wide analysis of FLNB. Our findings indicated that FLNB may play an important regulatory role in cancer cell apoptosis via the regulation of alternative splicing and potentially transcription, which greatly expands the current understanding of the mechanisms of FLNB mediated gene regulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE134769 | GEO | 2020/05/19

REPOSITORIES: GEO