ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells.
Yisa Song BaFei Wang MaYaxun Wei MaDong ChenGang Deng BaPublished in: Technology in cancer research & treatment (2022)
Background: Aberrant expression and alternative splicing of oncogenes are the driving events in tumor initiation and development. But how these events are regulated in cancer cells is largely unknown. Functions of ATP5A1, an important mitochondrial ATP synthase gene, in transcriptional and posttranscriptional regulation were explored in this study. Methods: ATP5A1 was overexpressed using plasmid-transformed HeLa cells, and its influence on cell apoptosis and proliferation is evaluated. Transcriptome sequencing was then performed using RNA-seq to study the changes in gene expression and regulation of alternative splicing events. Validation of the implicated genes was achieved using RT-qPCR analysis. Results: It was found that ATP5A1 could significantly promote cellular apoptosis, but it had no influence on cell proliferation. ATP5A1 overexpression significantly increased the expression levels of genes associated with the innate immune response, angiogenesis, and collagen catabolic processes. This included enrichment of MMP2 and MMP19. It was also found that ATP5A1 could interfere with the alternative splicing of hundreds of genes associated with glucose homeostasis, HIF-1 signaling activation, and several pathways associated with cancers. Eight ATP5A1-regulated differentially expressed genes and 3 genes altered by splicing were selected and validated using RT-qPCR analysis. Conclusions: In summary, we illustrate the regulatory functions of ATP5A1 on the transcriptome of HeLa cells by exploring its influence on gene expression and alternative splicing. The results suggest that ATP5A1 may play an important regulatory role in cervical cancer cells by regulating expression and alternative splicing of cancer-associated genes. This study provides novel insights into the current understanding of the mechanisms of ATP5A1 on carcinogenesis and cancer progression.
Keyphrases
- gene expression
- cell cycle arrest
- genome wide
- immune response
- rna seq
- cell proliferation
- poor prognosis
- transcription factor
- induced apoptosis
- single cell
- genome wide identification
- dna methylation
- cell death
- oxidative stress
- signaling pathway
- endoplasmic reticulum stress
- pi k akt
- adipose tissue
- escherichia coli
- blood pressure
- endothelial cells
- type diabetes
- metabolic syndrome
- young adults
- crispr cas
- cell cycle
- lymph node metastasis
- bioinformatics analysis
- insulin resistance
- dendritic cells
- heat shock protein