APEX1 regulates alternative splicing of key tumorigenesis genes in non-small-cell lung cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-02

AUTHORS

Li Peng, Yuwei Liu, Jing Chen, Mengxin Cheng, Ying Wu, Min Chen, Ya Zhong, Dan Shen, Ling Chen, Xujun Ye

ABSTRACT

BackgroundAberrant alternative splicing (AS) contributes to tumor progression. Previous studies have shown that apurinic-apyrimidinic endonuclease-1 (APEX1) is involved in tumor progression. It is unknown whether APEX1 functions in tumor progression by regulation of AS. It is also unknown whether APEX1 can regulate non-small-cell lung cancer (NSCLC) proliferation and apoptosis. We analyzed APEX1 expression levels in 517 lung NSCLC samples from the TCGA (Cancer Genome Atlas) database. The impact of APEX1 over expression on A549 cell proliferation and apoptosis was detected by the methyl thiazolyl tetrazolium assay and by flow cytometry. The transcriptome of A549 cells with and without APEX1 over expression was determined by Illumina sequencing, followed by analysis of AS. RT-qPCR validated expression of APEX1-related genes in A549 cells. We have successfully applied RNA-seq technology to demonstrate APEX1 regulation of AS.ResultsAPEX1 expression was shown to be upregulated in NSCLC samples and to reduce cell proliferation and induce apoptosis of A549 cells. In addition, APEX1 regulated AS of key tumorigenesis genes involved in cancer proliferation and apoptosis within MAPK and Wnt signaling pathways. Each of these pathways are involved in lung cancer progression. Furthermore, validated AS events regulated by APEX1 were in key tumorigenesis genes; AXIN1 (axis inhibition protein 1), GCNT2 (N-acetyl glucosaminyl transferase 2), and SMAD3 (SMAD Family Member 3). These genes encode signaling pathway transcription regulatory factors.ConclusionsWe found that increased expression of APEX1 was an independent prognostic factor related to NSCLC progression. Therefore, APEX1 regulation of AS may serve as a molecular marker or therapeutic target for NSCLC treatment. More... »

PAGES

147

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12920-022-01290-0

DOI

http://dx.doi.org/10.1186/s12920-022-01290-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1149185648

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35780128


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biological Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Biochemistry and Cell Biology", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Genetics", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Alternative Splicing", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Carcinoma, Non-Small-Cell Lung", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Cell Transformation, Neoplastic", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "DNA-(Apurinic or Apyrimidinic Site) Lyase", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Endonucleases", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Humans", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Lung Neoplasms", 
        "type": "DefinedTerm"
      }, 
      {
        "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
        "name": "Wnt Signaling Pathway", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Department of Cardiology, Zhongnan Hosipital of Wuhan University, Wuhan University, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.49470.3e", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
            "Department of Cardiology, Zhongnan Hosipital of Wuhan University, Wuhan University, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Peng", 
        "givenName": "Li", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Liu", 
        "givenName": "Yuwei", 
        "id": "sg:person.013227633062.21", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013227633062.21"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Jing", 
        "id": "sg:person.014025213462.94", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014025213462.94"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Cheng", 
        "givenName": "Mengxin", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Wu", 
        "givenName": "Ying", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Min", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Zhong", 
        "givenName": "Ya", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Shen", 
        "givenName": "Dan", 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Chen", 
        "givenName": "Ling", 
        "id": "sg:person.011105424662.20", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011105424662.20"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China", 
          "id": "http://www.grid.ac/institutes/grid.413247.7", 
          "name": [
            "Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Ye", 
        "givenName": "Xujun", 
        "id": "sg:person.011666375363.72", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011666375363.72"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "sg:pub.10.1038/onc.2013.533", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015787443", 
          "https://doi.org/10.1038/onc.2013.533"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nrm.2017.27", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1085377742", 
          "https://doi.org/10.1038/nrm.2017.27"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1245/s10434-012-2431-2", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1014960126", 
          "https://doi.org/10.1245/s10434-012-2431-2"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s12094-009-0353-7", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029443697", 
          "https://doi.org/10.1007/s12094-009-0353-7"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/onc.2015.318", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018683798", 
          "https://doi.org/10.1038/onc.2015.318"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s00408-020-00407-5", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1132536854", 
          "https://doi.org/10.1007/s00408-020-00407-5"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/s41573-019-0044-1", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1121612506", 
          "https://doi.org/10.1038/s41573-019-0044-1"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature25183", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1100588738", 
          "https://doi.org/10.1038/nature25183"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/gb-2013-14-4-r36", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015459845", 
          "https://doi.org/10.1186/gb-2013-14-4-r36"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.bjc.6605541", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1002297623", 
          "https://doi.org/10.1038/sj.bjc.6605541"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nature07509", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029002744", 
          "https://doi.org/10.1038/nature07509"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s12885-019-5671-8", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1115900535", 
          "https://doi.org/10.1186/s12885-019-5671-8"
        ], 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2022-07-02", 
    "datePublishedReg": "2022-07-02", 
    "description": "BackgroundAberrant alternative splicing (AS) contributes to tumor progression. Previous studies have shown that apurinic-apyrimidinic endonuclease-1 (APEX1) is involved in tumor progression. It is unknown whether APEX1 functions in tumor progression by regulation of AS. It is also unknown whether APEX1 can regulate non-small-cell lung cancer (NSCLC) proliferation and apoptosis. We analyzed APEX1 expression levels in 517 lung NSCLC samples from the TCGA (Cancer Genome Atlas) database. The impact of APEX1 over expression on A549 cell proliferation and apoptosis was detected by the methyl thiazolyl tetrazolium assay and by flow cytometry. The transcriptome of A549 cells with and without APEX1 over expression was determined by Illumina sequencing, followed by analysis of AS. RT-qPCR validated expression of APEX1-related genes in A549 cells. We have successfully applied RNA-seq technology to demonstrate APEX1 regulation of AS.ResultsAPEX1 expression was shown to be upregulated in NSCLC samples and to reduce cell proliferation and induce apoptosis of A549 cells. In addition, APEX1 regulated AS of key tumorigenesis genes involved in cancer proliferation and apoptosis within MAPK and Wnt signaling pathways. Each of these pathways are involved in lung cancer progression. Furthermore, validated AS events regulated by APEX1 were in key tumorigenesis genes; AXIN1 (axis inhibition protein 1), GCNT2 (N-acetyl glucosaminyl transferase 2), and SMAD3 (SMAD Family Member 3). These genes encode signaling pathway transcription regulatory factors.ConclusionsWe found that increased expression of APEX1 was an independent prognostic factor related to NSCLC progression. Therefore, APEX1 regulation of AS may serve as a molecular marker or therapeutic target for NSCLC treatment.", 
    "genre": "article", 
    "id": "sg:pub.10.1186/s12920-022-01290-0", 
    "isAccessibleForFree": true, 
    "isPartOf": [
      {
        "id": "sg:journal.1039191", 
        "issn": [
          "1755-8794"
        ], 
        "name": "BMC Medical Genomics", 
        "publisher": "Springer Nature", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "15"
      }
    ], 
    "keywords": [
      "alternative splicing", 
      "tumorigenesis genes", 
      "expression of APEX1", 
      "analysis of AS", 
      "regulation of AS", 
      "apurinic-apyrimidinic endonuclease 1", 
      "RNA-seq technology", 
      "A549 cells", 
      "cell proliferation", 
      "transcription regulatory factors", 
      "tumor progression", 
      "cancer proliferation", 
      "cell lung cancer proliferation", 
      "Illumina sequencing", 
      "A549 cell proliferation", 
      "lung cancer progression", 
      "regulatory factors", 
      "endonuclease 1", 
      "molecular markers", 
      "lung cancer proliferation", 
      "genes", 
      "methyl thiazolyl tetrazolium", 
      "cancer progression", 
      "APEX1", 
      "expression levels", 
      "splicing", 
      "apoptosis", 
      "NSCLC progression", 
      "NSCLC samples", 
      "RT-qPCR", 
      "TCGA database", 
      "regulation", 
      "expression", 
      "therapeutic target", 
      "proliferation", 
      "pathway", 
      "flow cytometry", 
      "cells", 
      "transcriptome", 
      "Wnt", 
      "AXIN1", 
      "MAPK", 
      "GCNT2", 
      "progression", 
      "sequencing", 
      "NSCLC treatment", 
      "Smad3", 
      "independent prognostic factor", 
      "cell lung cancer", 
      "previous studies", 
      "cytometry", 
      "prognostic factors", 
      "target", 
      "tetrazolium", 
      "markers", 
      "lung cancer", 
      "factors", 
      "function", 
      "cancer", 
      "events", 
      "levels", 
      "addition", 
      "analysis", 
      "treatment", 
      "samples", 
      "study", 
      "ConclusionsWe", 
      "database", 
      "impact", 
      "technology"
    ], 
    "name": "APEX1 regulates alternative splicing of key tumorigenesis genes in non-small-cell lung cancer", 
    "pagination": "147", 
    "productId": [
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1149185648"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1186/s12920-022-01290-0"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "35780128"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1186/s12920-022-01290-0", 
      "https://app.dimensions.ai/details/publication/pub.1149185648"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2022-09-02T16:08", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-springernature-scigraph/baseset/20220902/entities/gbq_results/article/article_942.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://doi.org/10.1186/s12920-022-01290-0"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/s12920-022-01290-0'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/s12920-022-01290-0'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/s12920-022-01290-0'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/s12920-022-01290-0'


 

This table displays all metadata directly associated to this object as RDF triples.

283 TRIPLES      21 PREDICATES      118 URIs      95 LITERALS      15 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1186/s12920-022-01290-0 schema:about N23f49699cced46b9ac3134be484b5b8e
2 N2def1023b284419fa1f2b90fe10a690f
3 N4922645e3c234ef48e17de4c16eb1ff7
4 N754c4ac13028415e93ac4ec1e0d1fca0
5 N89f19ee8ff9d439d819472438bcff957
6 Nc2c24e05a51741288554979077c21c4b
7 Nd30e0badadda4373bcf2ee483289061e
8 Ne59efe736741404c98a850c347dc80b6
9 anzsrc-for:06
10 anzsrc-for:0601
11 anzsrc-for:0604
12 anzsrc-for:11
13 anzsrc-for:1112
14 schema:author N0a88ba40886748e896143eb5e4e694fa
15 schema:citation sg:pub.10.1007/s00408-020-00407-5
16 sg:pub.10.1007/s12094-009-0353-7
17 sg:pub.10.1038/nature07509
18 sg:pub.10.1038/nature25183
19 sg:pub.10.1038/nrm.2017.27
20 sg:pub.10.1038/onc.2013.533
21 sg:pub.10.1038/onc.2015.318
22 sg:pub.10.1038/s41573-019-0044-1
23 sg:pub.10.1038/sj.bjc.6605541
24 sg:pub.10.1186/gb-2013-14-4-r36
25 sg:pub.10.1186/s12885-019-5671-8
26 sg:pub.10.1245/s10434-012-2431-2
27 schema:datePublished 2022-07-02
28 schema:datePublishedReg 2022-07-02
29 schema:description BackgroundAberrant alternative splicing (AS) contributes to tumor progression. Previous studies have shown that apurinic-apyrimidinic endonuclease-1 (APEX1) is involved in tumor progression. It is unknown whether APEX1 functions in tumor progression by regulation of AS. It is also unknown whether APEX1 can regulate non-small-cell lung cancer (NSCLC) proliferation and apoptosis. We analyzed APEX1 expression levels in 517 lung NSCLC samples from the TCGA (Cancer Genome Atlas) database. The impact of APEX1 over expression on A549 cell proliferation and apoptosis was detected by the methyl thiazolyl tetrazolium assay and by flow cytometry. The transcriptome of A549 cells with and without APEX1 over expression was determined by Illumina sequencing, followed by analysis of AS. RT-qPCR validated expression of APEX1-related genes in A549 cells. We have successfully applied RNA-seq technology to demonstrate APEX1 regulation of AS.ResultsAPEX1 expression was shown to be upregulated in NSCLC samples and to reduce cell proliferation and induce apoptosis of A549 cells. In addition, APEX1 regulated AS of key tumorigenesis genes involved in cancer proliferation and apoptosis within MAPK and Wnt signaling pathways. Each of these pathways are involved in lung cancer progression. Furthermore, validated AS events regulated by APEX1 were in key tumorigenesis genes; AXIN1 (axis inhibition protein 1), GCNT2 (N-acetyl glucosaminyl transferase 2), and SMAD3 (SMAD Family Member 3). These genes encode signaling pathway transcription regulatory factors.ConclusionsWe found that increased expression of APEX1 was an independent prognostic factor related to NSCLC progression. Therefore, APEX1 regulation of AS may serve as a molecular marker or therapeutic target for NSCLC treatment.
30 schema:genre article
31 schema:isAccessibleForFree true
32 schema:isPartOf N6daaec20edbe4923acad55009fc38af3
33 Nd0144c91918841989eac90b2fbc7194f
34 sg:journal.1039191
35 schema:keywords A549 cell proliferation
36 A549 cells
37 APEX1
38 AXIN1
39 ConclusionsWe
40 GCNT2
41 Illumina sequencing
42 MAPK
43 NSCLC progression
44 NSCLC samples
45 NSCLC treatment
46 RNA-seq technology
47 RT-qPCR
48 Smad3
49 TCGA database
50 Wnt
51 addition
52 alternative splicing
53 analysis
54 analysis of AS
55 apoptosis
56 apurinic-apyrimidinic endonuclease 1
57 cancer
58 cancer progression
59 cancer proliferation
60 cell lung cancer
61 cell lung cancer proliferation
62 cell proliferation
63 cells
64 cytometry
65 database
66 endonuclease 1
67 events
68 expression
69 expression levels
70 expression of APEX1
71 factors
72 flow cytometry
73 function
74 genes
75 impact
76 independent prognostic factor
77 levels
78 lung cancer
79 lung cancer progression
80 lung cancer proliferation
81 markers
82 methyl thiazolyl tetrazolium
83 molecular markers
84 pathway
85 previous studies
86 prognostic factors
87 progression
88 proliferation
89 regulation
90 regulation of AS
91 regulatory factors
92 samples
93 sequencing
94 splicing
95 study
96 target
97 technology
98 tetrazolium
99 therapeutic target
100 transcription regulatory factors
101 transcriptome
102 treatment
103 tumor progression
104 tumorigenesis genes
105 schema:name APEX1 regulates alternative splicing of key tumorigenesis genes in non-small-cell lung cancer
106 schema:pagination 147
107 schema:productId N2687ce3aa0ce4cb7a9f821b8fb666d56
108 N376e11b3c4d74daf83cca9b78fcb19e9
109 Ncd13f39ab4b74d00bfa0133aa93fb5cb
110 schema:sameAs https://app.dimensions.ai/details/publication/pub.1149185648
111 https://doi.org/10.1186/s12920-022-01290-0
112 schema:sdDatePublished 2022-09-02T16:08
113 schema:sdLicense https://scigraph.springernature.com/explorer/license/
114 schema:sdPublisher N51ac717513904ee4ae5589731470a311
115 schema:url https://doi.org/10.1186/s12920-022-01290-0
116 sgo:license sg:explorer/license/
117 sgo:sdDataset articles
118 rdf:type schema:ScholarlyArticle
119 N0a88ba40886748e896143eb5e4e694fa rdf:first Nd7d480f81d184053ac7312a7b2490304
120 rdf:rest N717dab0b3fed4eb2ba826bebc3986a5a
121 N0cb81ae3ea4645f0abae19329adf7e7b schema:affiliation grid-institutes:grid.413247.7
122 schema:familyName Shen
123 schema:givenName Dan
124 rdf:type schema:Person
125 N1ab6ec68726e420894e41c6375e36a0c rdf:first sg:person.011666375363.72
126 rdf:rest rdf:nil
127 N23f49699cced46b9ac3134be484b5b8e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
128 schema:name Alternative Splicing
129 rdf:type schema:DefinedTerm
130 N2687ce3aa0ce4cb7a9f821b8fb666d56 schema:name doi
131 schema:value 10.1186/s12920-022-01290-0
132 rdf:type schema:PropertyValue
133 N2def1023b284419fa1f2b90fe10a690f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
134 schema:name Cell Transformation, Neoplastic
135 rdf:type schema:DefinedTerm
136 N376e11b3c4d74daf83cca9b78fcb19e9 schema:name dimensions_id
137 schema:value pub.1149185648
138 rdf:type schema:PropertyValue
139 N44a9a45123e94710a62eb0b59906ab6e schema:affiliation grid-institutes:grid.413247.7
140 schema:familyName Cheng
141 schema:givenName Mengxin
142 rdf:type schema:Person
143 N4922645e3c234ef48e17de4c16eb1ff7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
144 schema:name Wnt Signaling Pathway
145 rdf:type schema:DefinedTerm
146 N51ac717513904ee4ae5589731470a311 schema:name Springer Nature - SN SciGraph project
147 rdf:type schema:Organization
148 N5325bb59b8534e118e7e13da3f93a57f rdf:first Nb513f9b52bc74f068bdee4942e171dee
149 rdf:rest Ne97224c175114dd8bae39d3766bf0008
150 N676ce0c204b64b76a6137f4293acf94b rdf:first sg:person.014025213462.94
151 rdf:rest Nf34401ee017047e28dde85ce7007e57a
152 N6daaec20edbe4923acad55009fc38af3 schema:volumeNumber 15
153 rdf:type schema:PublicationVolume
154 N717dab0b3fed4eb2ba826bebc3986a5a rdf:first sg:person.013227633062.21
155 rdf:rest N676ce0c204b64b76a6137f4293acf94b
156 N754c4ac13028415e93ac4ec1e0d1fca0 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
157 schema:name Humans
158 rdf:type schema:DefinedTerm
159 N77f5b0ae29ea4f78a39a177c11570eb8 schema:affiliation grid-institutes:grid.413247.7
160 schema:familyName Zhong
161 schema:givenName Ya
162 rdf:type schema:Person
163 N89f19ee8ff9d439d819472438bcff957 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
164 schema:name Endonucleases
165 rdf:type schema:DefinedTerm
166 N997a59c4688c40799345847e8225b994 schema:affiliation grid-institutes:grid.413247.7
167 schema:familyName Wu
168 schema:givenName Ying
169 rdf:type schema:Person
170 Nac15d17c363a4ae0a327d0fe13c9acbc rdf:first sg:person.011105424662.20
171 rdf:rest N1ab6ec68726e420894e41c6375e36a0c
172 Nb513f9b52bc74f068bdee4942e171dee schema:affiliation grid-institutes:grid.413247.7
173 schema:familyName Chen
174 schema:givenName Min
175 rdf:type schema:Person
176 Nbd2bbf604ea74ea2a21a31fe3bb44469 rdf:first N0cb81ae3ea4645f0abae19329adf7e7b
177 rdf:rest Nac15d17c363a4ae0a327d0fe13c9acbc
178 Nc2c24e05a51741288554979077c21c4b schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
179 schema:name DNA-(Apurinic or Apyrimidinic Site) Lyase
180 rdf:type schema:DefinedTerm
181 Ncba747fc61af4b06aa1b21bb377d9de9 rdf:first N997a59c4688c40799345847e8225b994
182 rdf:rest N5325bb59b8534e118e7e13da3f93a57f
183 Ncd13f39ab4b74d00bfa0133aa93fb5cb schema:name pubmed_id
184 schema:value 35780128
185 rdf:type schema:PropertyValue
186 Nd0144c91918841989eac90b2fbc7194f schema:issueNumber 1
187 rdf:type schema:PublicationIssue
188 Nd30e0badadda4373bcf2ee483289061e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
189 schema:name Carcinoma, Non-Small-Cell Lung
190 rdf:type schema:DefinedTerm
191 Nd7d480f81d184053ac7312a7b2490304 schema:affiliation grid-institutes:grid.49470.3e
192 schema:familyName Peng
193 schema:givenName Li
194 rdf:type schema:Person
195 Ne59efe736741404c98a850c347dc80b6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
196 schema:name Lung Neoplasms
197 rdf:type schema:DefinedTerm
198 Ne97224c175114dd8bae39d3766bf0008 rdf:first N77f5b0ae29ea4f78a39a177c11570eb8
199 rdf:rest Nbd2bbf604ea74ea2a21a31fe3bb44469
200 Nf34401ee017047e28dde85ce7007e57a rdf:first N44a9a45123e94710a62eb0b59906ab6e
201 rdf:rest Ncba747fc61af4b06aa1b21bb377d9de9
202 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
203 schema:name Biological Sciences
204 rdf:type schema:DefinedTerm
205 anzsrc-for:0601 schema:inDefinedTermSet anzsrc-for:
206 schema:name Biochemistry and Cell Biology
207 rdf:type schema:DefinedTerm
208 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
209 schema:name Genetics
210 rdf:type schema:DefinedTerm
211 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
212 schema:name Medical and Health Sciences
213 rdf:type schema:DefinedTerm
214 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
215 schema:name Oncology and Carcinogenesis
216 rdf:type schema:DefinedTerm
217 sg:journal.1039191 schema:issn 1755-8794
218 schema:name BMC Medical Genomics
219 schema:publisher Springer Nature
220 rdf:type schema:Periodical
221 sg:person.011105424662.20 schema:affiliation grid-institutes:grid.413247.7
222 schema:familyName Chen
223 schema:givenName Ling
224 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011105424662.20
225 rdf:type schema:Person
226 sg:person.011666375363.72 schema:affiliation grid-institutes:grid.413247.7
227 schema:familyName Ye
228 schema:givenName Xujun
229 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.011666375363.72
230 rdf:type schema:Person
231 sg:person.013227633062.21 schema:affiliation grid-institutes:grid.413247.7
232 schema:familyName Liu
233 schema:givenName Yuwei
234 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.013227633062.21
235 rdf:type schema:Person
236 sg:person.014025213462.94 schema:affiliation grid-institutes:grid.413247.7
237 schema:familyName Chen
238 schema:givenName Jing
239 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.014025213462.94
240 rdf:type schema:Person
241 sg:pub.10.1007/s00408-020-00407-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1132536854
242 https://doi.org/10.1007/s00408-020-00407-5
243 rdf:type schema:CreativeWork
244 sg:pub.10.1007/s12094-009-0353-7 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029443697
245 https://doi.org/10.1007/s12094-009-0353-7
246 rdf:type schema:CreativeWork
247 sg:pub.10.1038/nature07509 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029002744
248 https://doi.org/10.1038/nature07509
249 rdf:type schema:CreativeWork
250 sg:pub.10.1038/nature25183 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100588738
251 https://doi.org/10.1038/nature25183
252 rdf:type schema:CreativeWork
253 sg:pub.10.1038/nrm.2017.27 schema:sameAs https://app.dimensions.ai/details/publication/pub.1085377742
254 https://doi.org/10.1038/nrm.2017.27
255 rdf:type schema:CreativeWork
256 sg:pub.10.1038/onc.2013.533 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015787443
257 https://doi.org/10.1038/onc.2013.533
258 rdf:type schema:CreativeWork
259 sg:pub.10.1038/onc.2015.318 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018683798
260 https://doi.org/10.1038/onc.2015.318
261 rdf:type schema:CreativeWork
262 sg:pub.10.1038/s41573-019-0044-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1121612506
263 https://doi.org/10.1038/s41573-019-0044-1
264 rdf:type schema:CreativeWork
265 sg:pub.10.1038/sj.bjc.6605541 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002297623
266 https://doi.org/10.1038/sj.bjc.6605541
267 rdf:type schema:CreativeWork
268 sg:pub.10.1186/gb-2013-14-4-r36 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015459845
269 https://doi.org/10.1186/gb-2013-14-4-r36
270 rdf:type schema:CreativeWork
271 sg:pub.10.1186/s12885-019-5671-8 schema:sameAs https://app.dimensions.ai/details/publication/pub.1115900535
272 https://doi.org/10.1186/s12885-019-5671-8
273 rdf:type schema:CreativeWork
274 sg:pub.10.1245/s10434-012-2431-2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1014960126
275 https://doi.org/10.1245/s10434-012-2431-2
276 rdf:type schema:CreativeWork
277 grid-institutes:grid.413247.7 schema:alternateName Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China
278 schema:name Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China
279 rdf:type schema:Organization
280 grid-institutes:grid.49470.3e schema:alternateName Department of Cardiology, Zhongnan Hosipital of Wuhan University, Wuhan University, 430071, Wuhan, Hubei, China
281 schema:name Department of Cardiology, Zhongnan Hosipital of Wuhan University, Wuhan University, 430071, Wuhan, Hubei, China
282 Department of Internal Medicine and Geriatrics, Zhongnan Hospital of Wuhan University, Wuhan University, No. 169 Dong Hu Road, 430071, Wuhan, Hubei, China
283 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...