Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
December-2016 Volume 36 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2016 Volume 36 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells

  • Authors:
    • Ángela L. Riffo-Campos
    • Josefa Castillo
    • Azahara Vallet-Sánchez
    • Guillermo Ayala
    • Andrés Cervantes
    • Gerardo López-Rodas
    • Luis Franco
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry and Molecular Biology, University of Valencia, Valencia, Spain, INCLIVA Institute of Health Research, Valencia, Spain, Department of Statistics and Operational Research, University of Valencia, Burjassot, Valencia, Spain
  • Pages: 3627-3634
    |
    Published online on: October 27, 2016
       https://doi.org/10.3892/or.2016.5210
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Several drugs used for the treatment of colorectal cancer (CRC) are targeted at the epidermal growth factor receptor, but mutations in genes of the RAS family cause resistance to these drugs. Thus, extensive research is being carried out to counterbalance this resistance. The G13D mutation of KRAS is common in humans, and we previously reported that this mutation results in the epigenetic modification of hnRNP proteins, involved in RNA splicing. As aberrant splicing often results in oncogenicity, the present study aimed to identify the genes which show altered splicing patterns in connection with the G13D KRAS mutation. To accomplish this, we first carried out an in silico analysis of RNA-seq databases and found that the distribution of alternative splicing isoforms of genes RPL13, HSP90B1, ENO1, EPDR1 and ZNF518B was altered in human CRC cell lines carrying the G13D KRAS mutation when compared to cell lines carrying wild-type KRAS. The in silico results were experimentally validated by quantitative real‑time PCR. Expression of the genes EPDR1 and ZNF518B was negligible in the Caco2, RKO and SW48 cell lines, which possess wild-type KRAS, while the HCT116, DLD1 and D-Mut1 cell lines, harbouring the G13D mutation, expressed these genes. Moreover, in both genes, the ratio of isoforms was significantly different between the parental DLD1 (+/G13D) and D-Mut1 cells, in which the wild-type allele had been knocked out. DWT7m cells also expressed both genes. These cells, derived from DLD1, have spontaneously acquired a G12D mutation in their single KRAS allele in 20% of the population. The present data suggest a relationship between KRAS mutations, particularly G13D, and the expression of the EPDR1 and ZNF518B genes and expression of their isoforms and provide enhanced understanding of the molecular mechanisms involved in the resistance of CRC cells to anti‑EGF receptor therapies.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Stewart BW and Wild CP: World Cancer Report 2014. IARC Publications; Lyon: 2014

2 

Wong A and Ma BBY: Personalizing therapy for colorectal cancer. Clin Gastroenterol Hepatol. 12:139–144. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Van Cutsem E, Cervantes A, Nordlinger B and Arnold D: ESMO Guidelines Working Group: Metastatic colorectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 25:(Suppl 3). iii1–iii9. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Brand TM, Iida M and Wheeler DL: Molecular mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Cancer Biol Ther. 11:777–792. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Prior IA, Lewis PD and Mattos C: A comprehensive survey of Ras mutations in cancer. Cancer Res. 72:2457–2467. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Schubbert S, Shannon K and Bollag G: Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 7:295–308. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Dócs O, Fazakas F, Horváth NL, Tóth L, András C, Horváth Z and Méhes G: Changes of KRAS exon 2 codon 12/13 mutation status in recurrent colorectal cancer. Pathol Oncol Res. 21:399–404. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Roda D, Castillo J, Telechea-Fernández M, Gil A, López-Rodas G, Franco L, González-Rodríguez P, Roselló S, Pérez-Fidalgo JA, García-Trevijano ER, et al: EGF-induced acetylation of heterogeneous nuclear ribonucleoproteins is dependent on KRAS mutational status in colorectal cancer cells. PLoS One. 10:e01305432015. View Article : Google Scholar : PubMed/NCBI

9 

Soh J, Okumura N, Lockwood WW, Yamamoto H, Shigematsu H, Zhang W, Chari R, Shames DS, Tang X, MacAulay C, et al: Oncogene mutations, copy number gains and mutant allele specific imbalance (MASI) frequently occur together in tumor cells. PLoS One. 4:e74642009. View Article : Google Scholar : PubMed/NCBI

10 

Hartman DJ, Davison JM, Foxwell TJ, Nikiforova MN and Chiosea SI: Mutant allele-specific imbalance modulates prognostic impact of KRAS mutations in colorectal adenocarcinoma and is associated with worse overall survival. Int J Cancer. 131:1810–1817. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Malapelle U, Sgariglia R, De Stefano A, Bellevicine C, Vigliar E, de Biase D, Sepe R, Pallante P, Carlomagno C, Tallini G, et al: KRAS mutant allele-specific imbalance (MASI) assessment in routine samples of patients with metastatic colorectal cancer. J Clin Pathol. 68:265–269. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Costa V, Aprile M, Esposito R and Ciccodicola A: RNA-Seq and human complex diseases: Recent accomplishments and future perspectives. Eur J Hum Genet. 21:134–142. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Du J and Zhang L: Integrated analysis of DNA methylation and microRNA regulation of the lung adenocarcinoma transcriptome. Oncol Rep. 34:585–594. 2015.PubMed/NCBI

14 

Panagopoulos I, Gorunova L, Zeller B, Tierens A and Heim S: Cryptic FUS-ERG fusion identified by RNA-sequencing in childhood acute myeloid leukemia. Oncol Rep. 30:2587–2592. 2013.PubMed/NCBI

15 

Wang W, Qin Z, Feng Z, Wang X and Zhang X: Identifying differentially spliced genes from two groups of RNA-seq samples. Gene. 518:164–170. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Wang ET, Sandberg R, Luo S, Khrebtukova I, Zhang L, Mayr C, Kingsmore SF, Schroth GP and Burge CB: Alternative isoform regulation in human tissue transcriptomes. Nature. 456:470–476. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Matera AG and Wang Z: A day in the life of the spliceosome. Nat Rev Mol Cell Biol. 15:108–121. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Ladomery M: Aberrant alternative splicing is another hallmark of cancer. Int J Cell Biol. 2013:4637862013. View Article : Google Scholar : PubMed/NCBI

19 

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G and Durbin R: 1000 Genome Project Data Processing Subgroup: The Sequence Alignment/Map format and SAMtools. Bioinformatics. 25:2078–2079. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ and Pachter L: Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol. 28:511–515. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Vitting-Seerup K, Porse BT, Sandelin A and Waage J: spliceR: An R package for classification of alternative splicing and prediction of coding potential from RNA-seq data. BMC Bioinformatics. 15:812014. View Article : Google Scholar : PubMed/NCBI

22 

Simms D, Cizdziel P and Chomczynski P: TRIzol: A new reagent for optimal single-step isolation of RNA. Focus. 15:99–102. 1993.

23 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Slattery ML, Pellatt DF, Mullany LE, Wolff RK and Herrick JS: Gene expression in colon cancer: A focus on tumor site and molecular phenotype. Genes Chromosomes Cancer. 54:527–541. 2015. View Article : Google Scholar : PubMed/NCBI

25 

Shashoua VE: The role of brain extracellular proteins in neuroplasticity and learning. Cell Mol Neurobiol. 5:183–207. 1985. View Article : Google Scholar : PubMed/NCBI

26 

Nimmrich I, Erdmann S, Melchers U, Chtarbova S, Finke U, Hentsch S, Hoffmann I, Oertel M, Hoffmann W and Müller O: The novel ependymin related gene UCC1 is highly expressed in colorectal tumor cells. Cancer Lett. 165:71–79. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Pradel G, Schachner M and Schmidt R: Inhibition of memory consolidation by antibodies against cell adhesion molecules after active avoidance conditioning in zebrafish. J Neurobiol. 39:197–206. 1999. View Article : Google Scholar : PubMed/NCBI

28 

Hoffmann W and Schwarz H: Ependymins: Meningeal-derived extracellular matrix proteins at the blood-brain barrier. Int Rev Cytol. 165:121–158. 1996. View Article : Google Scholar : PubMed/NCBI

29 

Shashoua VE, Adams D and Boyer-Boiteau A: CMX-8933, a peptide fragment of the glycoprotein ependymin, promotes activation of AP-1 transcription factor in mouse neuroblastoma and rat cortical cell cultures. Neurosci Lett. 312:103–107. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Jin TB, Ren Y, Shi X, Jiri M, He N, Feng T, Yuan D and Kang L: Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case-control sample sets. Rheumatol Int. 35:1141–1147. 2015. View Article : Google Scholar : PubMed/NCBI

31 

Zhang XY, Geng TT, Liu LJ, Yuan DY, Feng T, Kang LL, Jin TB and Chen C: SLC2A9 and ZNF518B polymorphisms correlate with gout-related metabolic indices in Chinese Tibetan populations. Genet Mol Res. 14:9915–9921. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Maier VK, Feeney CM, Taylor JE, Creech AL, Qiao JW, Szanto A, Das PP, Chevrier N, Cifuentes-Rojas C, Orkin SH, et al: Functional proteomic analysis of repressive histone methyltransferase complexes PRC2 and G9A reveals ZNF518B as a G9A regulator. Mol Cell Proteomics. 14:1435–1446. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Shankar SR, Bahirvani AG, Rao VK, Bharathy N, Ow JR and Taneja R: G9a, a multipotent regulator of gene expression. Epigenetics. 8:16–22. 2013. View Article : Google Scholar : PubMed/NCBI

34 

Zhao Z, Wang D, Zhu C, Shao H, Sun C, Qiu H, Xue L, Xu J, Guo M and Li W: Aberrant alternative splicing of human zinc finger gene ZNF268 in human hematological malignancy. Oncol Rep. 20:1243–1248. 2008.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Riffo-Campos ÁL, Castillo J, Vallet-Sánchez A, Ayala G, Cervantes A, López-Rodas G and Franco L: In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells. Oncol Rep 36: 3627-3634, 2016.
APA
Riffo-Campos, Á.L., Castillo, J., Vallet-Sánchez, A., Ayala, G., Cervantes, A., López-Rodas, G., & Franco, L. (2016). In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells. Oncology Reports, 36, 3627-3634. https://doi.org/10.3892/or.2016.5210
MLA
Riffo-Campos, Á. L., Castillo, J., Vallet-Sánchez, A., Ayala, G., Cervantes, A., López-Rodas, G., Franco, L."In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells". Oncology Reports 36.6 (2016): 3627-3634.
Chicago
Riffo-Campos, Á. L., Castillo, J., Vallet-Sánchez, A., Ayala, G., Cervantes, A., López-Rodas, G., Franco, L."In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells". Oncology Reports 36, no. 6 (2016): 3627-3634. https://doi.org/10.3892/or.2016.5210
Copy and paste a formatted citation
x
Spandidos Publications style
Riffo-Campos ÁL, Castillo J, Vallet-Sánchez A, Ayala G, Cervantes A, López-Rodas G and Franco L: In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells. Oncol Rep 36: 3627-3634, 2016.
APA
Riffo-Campos, Á.L., Castillo, J., Vallet-Sánchez, A., Ayala, G., Cervantes, A., López-Rodas, G., & Franco, L. (2016). In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells. Oncology Reports, 36, 3627-3634. https://doi.org/10.3892/or.2016.5210
MLA
Riffo-Campos, Á. L., Castillo, J., Vallet-Sánchez, A., Ayala, G., Cervantes, A., López-Rodas, G., Franco, L."In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells". Oncology Reports 36.6 (2016): 3627-3634.
Chicago
Riffo-Campos, Á. L., Castillo, J., Vallet-Sánchez, A., Ayala, G., Cervantes, A., López-Rodas, G., Franco, L."In silico RNA-seq and experimental analyses reveal the differential expression and splicing of EPDR1 and ZNF518B genes in relation to KRAS mutations in colorectal cancer cells". Oncology Reports 36, no. 6 (2016): 3627-3634. https://doi.org/10.3892/or.2016.5210
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team