Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients

Background: Skin cancer represents the most common human malignancy, and it includes BCC, SCC, and melanoma. Since melanoma is one of the most aggressive types of cancer, we have herein attempted to develop a gene-specific intron retention signature that can distinguish BCC and SCC from melanoma bio...

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Main Authors: Aikaterini F. Giannopoulou, Eumorphia G. Konstantakou, Athanassios D. Velentzas, Socratis N. Avgeris, Margaritis Avgeris, Nikos C. Papandreou, Ilianna Zoi, Vicky Filippa, Stamatia Katarachia, Antonis D. Lampidonis, Anastasia Prombona, Popi Syntichaki, Christina Piperi, Efthimia K. Basdra, Vassiliki Iconomidou, Evangelia Papadavid, Ema Anastasiadou, Issidora S. Papassideri, Athanasios G. Papavassiliou, Gerassimos E. Voutsinas, Andreas Scorilas, Dimitrios J. Stravopodis
Format: Article
Language:English
Published: MDPI AG 2019-02-01
Series:International Journal of Molecular Sciences
Subjects:
BCC
SCC
Online Access:https://www.mdpi.com/1422-0067/20/4/937
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author Aikaterini F. Giannopoulou
Eumorphia G. Konstantakou
Athanassios D. Velentzas
Socratis N. Avgeris
Margaritis Avgeris
Nikos C. Papandreou
Ilianna Zoi
Vicky Filippa
Stamatia Katarachia
Antonis D. Lampidonis
Anastasia Prombona
Popi Syntichaki
Christina Piperi
Efthimia K. Basdra
Vassiliki Iconomidou
Evangelia Papadavid
Ema Anastasiadou
Issidora S. Papassideri
Athanasios G. Papavassiliou
Gerassimos E. Voutsinas
Andreas Scorilas
Dimitrios J. Stravopodis
spellingShingle Aikaterini F. Giannopoulou
Eumorphia G. Konstantakou
Athanassios D. Velentzas
Socratis N. Avgeris
Margaritis Avgeris
Nikos C. Papandreou
Ilianna Zoi
Vicky Filippa
Stamatia Katarachia
Antonis D. Lampidonis
Anastasia Prombona
Popi Syntichaki
Christina Piperi
Efthimia K. Basdra
Vassiliki Iconomidou
Evangelia Papadavid
Ema Anastasiadou
Issidora S. Papassideri
Athanasios G. Papavassiliou
Gerassimos E. Voutsinas
Andreas Scorilas
Dimitrios J. Stravopodis
Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients
International Journal of Molecular Sciences
BCC
cancer
intron
melanoma
SCC
splicing
transcription
author_facet Aikaterini F. Giannopoulou
Eumorphia G. Konstantakou
Athanassios D. Velentzas
Socratis N. Avgeris
Margaritis Avgeris
Nikos C. Papandreou
Ilianna Zoi
Vicky Filippa
Stamatia Katarachia
Antonis D. Lampidonis
Anastasia Prombona
Popi Syntichaki
Christina Piperi
Efthimia K. Basdra
Vassiliki Iconomidou
Evangelia Papadavid
Ema Anastasiadou
Issidora S. Papassideri
Athanasios G. Papavassiliou
Gerassimos E. Voutsinas
Andreas Scorilas
Dimitrios J. Stravopodis
author_sort Aikaterini F. Giannopoulou
title Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients
title_short Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients
title_full Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients
title_fullStr Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients
title_full_unstemmed Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek Patients
title_sort gene-specific intron retention serves as molecular signature that distinguishes melanoma from non-melanoma cancer cells in greek patients
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1422-0067
publishDate 2019-02-01
description Background: Skin cancer represents the most common human malignancy, and it includes BCC, SCC, and melanoma. Since melanoma is one of the most aggressive types of cancer, we have herein attempted to develop a gene-specific intron retention signature that can distinguish BCC and SCC from melanoma biopsy tumors. Methods: Intron retention events were examined through RT-sqPCR protocols, using total RNA preparations derived from BCC, SCC, and melanoma Greek biopsy specimens. Intron-hosted miRNA species and their target transcripts were predicted via the miRbase and miRDB bioinformatics platforms, respectively. &#921;ntronic ORFs were recognized through the ORF Finder application. Generation and visualization of protein interactomes were achieved by the IntAct and Cytoscape softwares, while tertiary protein structures were produced by using the I-TASSER online server. Results: <i>c-MYC</i> and <i>Sestrin-1</i> genes proved to undergo intron retention specifically in melanoma. Interaction maps of proteins encoded by genes being potentially targeted by retained intron-accommodated miRNAs were generated and <i>SRPX2</i> was additionally delivered to our melanoma-specific signature. Novel ORFs were identified in <i>MCT4</i> and <i>Sestrin-1</i> introns, with potentially critical roles in melanoma development. Conclusions: The property of <i>c-MYC</i>, <i>Sestrin-1</i>, and <i>SRPX2</i> genes to retain specific introns could be clinically used to molecularly differentiate non-melanoma from melanoma tumors.
topic BCC
cancer
intron
melanoma
SCC
splicing
transcription
url https://www.mdpi.com/1422-0067/20/4/937
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spelling doaj-ed11c2f6e4f14023b0dc2b60b609ceef2020-11-25T01:33:16ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-02-0120493710.3390/ijms20040937ijms20040937Gene-Specific Intron Retention Serves as Molecular Signature that Distinguishes Melanoma from Non-Melanoma Cancer Cells in Greek PatientsAikaterini F. Giannopoulou0Eumorphia G. Konstantakou1Athanassios D. Velentzas2Socratis N. Avgeris3Margaritis Avgeris4Nikos C. Papandreou5Ilianna Zoi6Vicky Filippa7Stamatia Katarachia8Antonis D. Lampidonis9Anastasia Prombona10Popi Syntichaki11Christina Piperi12Efthimia K. Basdra13Vassiliki Iconomidou14Evangelia Papadavid15Ema Anastasiadou16Issidora S. Papassideri17Athanasios G. Papavassiliou18Gerassimos E. Voutsinas19Andreas Scorilas20Dimitrios J. Stravopodis21Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceLaboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research “Demokritos”, 15310 Athens, GreeceSection of Biochemistry and Molecular Biology, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceCenter of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceLaboratory of Chronobiology, Institute of Biosciences and Applications, National Center for Scientific Research “Demokritos”, 15310 Athens, GreeceCenter of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, GreeceDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece2nd Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, “Attikon” University Hospital, 12462 Athens, GreeceCenter of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, GreeceLaboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research “Demokritos”, 15310 Athens, GreeceSection of Biochemistry and Molecular Biology, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceSection of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, GreeceBackground: Skin cancer represents the most common human malignancy, and it includes BCC, SCC, and melanoma. Since melanoma is one of the most aggressive types of cancer, we have herein attempted to develop a gene-specific intron retention signature that can distinguish BCC and SCC from melanoma biopsy tumors. Methods: Intron retention events were examined through RT-sqPCR protocols, using total RNA preparations derived from BCC, SCC, and melanoma Greek biopsy specimens. Intron-hosted miRNA species and their target transcripts were predicted via the miRbase and miRDB bioinformatics platforms, respectively. &#921;ntronic ORFs were recognized through the ORF Finder application. Generation and visualization of protein interactomes were achieved by the IntAct and Cytoscape softwares, while tertiary protein structures were produced by using the I-TASSER online server. Results: <i>c-MYC</i> and <i>Sestrin-1</i> genes proved to undergo intron retention specifically in melanoma. Interaction maps of proteins encoded by genes being potentially targeted by retained intron-accommodated miRNAs were generated and <i>SRPX2</i> was additionally delivered to our melanoma-specific signature. Novel ORFs were identified in <i>MCT4</i> and <i>Sestrin-1</i> introns, with potentially critical roles in melanoma development. Conclusions: The property of <i>c-MYC</i>, <i>Sestrin-1</i>, and <i>SRPX2</i> genes to retain specific introns could be clinically used to molecularly differentiate non-melanoma from melanoma tumors.https://www.mdpi.com/1422-0067/20/4/937BCCcancerintronmelanomaSCCsplicingtranscription