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ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells
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 posttrans...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445539/ https://www.ncbi.nlm.nih.gov/pubmed/34520292 http://dx.doi.org/10.1177/15330338211039126 |
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author | Song, BA, Yisa Wang, MA, Fei Wei, MA, Yaxun Chen, BA, Dong Deng, BA, Gang |
author_facet | Song, BA, Yisa Wang, MA, Fei Wei, MA, Yaxun Chen, BA, Dong Deng, BA, Gang |
author_sort | Song, BA, Yisa |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8445539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-84455392021-09-17 ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells Song, BA, Yisa Wang, MA, Fei Wei, MA, Yaxun Chen, BA, Dong Deng, BA, Gang Technol Cancer Res Treat Original Article 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. SAGE Publications 2021-09-14 /pmc/articles/PMC8445539/ /pubmed/34520292 http://dx.doi.org/10.1177/15330338211039126 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Original Article Song, BA, Yisa Wang, MA, Fei Wei, MA, Yaxun Chen, BA, Dong Deng, BA, Gang ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells |
title | ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells |
title_full | ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells |
title_fullStr | ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells |
title_full_unstemmed | ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells |
title_short | ATP5A1 Participates in Transcriptional and Posttranscriptional Regulation of Cancer-Associated Genes by Modulating Their Expression and Alternative Splicing Profiles in HeLa Cells |
title_sort | atp5a1 participates in transcriptional and posttranscriptional regulation of cancer-associated genes by modulating their expression and alternative splicing profiles in hela cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445539/ https://www.ncbi.nlm.nih.gov/pubmed/34520292 http://dx.doi.org/10.1177/15330338211039126 |
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