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Int J Mol Sci. 2019 Feb 21;20(4). pii: E937. doi: 10.3390/ijms20040937.

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

Author information

1
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. Katia_13g@hotmail.com.
2
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. EKONSTANTAKOU@mgh.harvard.edu.
3
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. tveletz@biol.uoa.gr.
4
Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece. savgeris@bio.demokritos.gr.
5
Section of Biochemistry and Molecular Biology, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. margaritis.avgeris@gmail.com.
6
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. npapand@biol.uoa.gr.
7
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece. ilianna.zoi@gmail.com.
8
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece. vickyrougefilippa@gmail.com.
9
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. skatarachia@biol.uoa.gr.
10
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. labant@aua.gr.
11
Laboratory of Chronobiology, Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece. prombona@bio.demokritos.gr.
12
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece. synticha@bioacademy.gr.
13
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece. cpiperi@otenet.gr.
14
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece. ebasdra@med.uoa.gr.
15
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. veconom@biol.uoa.gr.
16
2nd Department of Dermatology and Venereology, Medical School, National and Kapodistrian University of Athens, "Attikon" University Hospital, 12462 Athens, Greece. epapad@med.uoa.gr.
17
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece. anastasiadou@bioacademy.gr.
18
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. ipapasid@biol.uoa.gr.
19
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece. papavas@med.uoa.gr.
20
Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", 15310 Athens, Greece. mvoutsin@bio.demokritos.gr.
21
Section of Biochemistry and Molecular Biology, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. ascorilas@biol.uoa.gr.
22
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens, 15701 Athens, Greece. dstravop@biol.uoa.gr.

Abstract

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. Ιntronic 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:

c-MYC and Sestrin-1 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 SRPX2 was additionally delivered to our melanoma-specific signature. Novel ORFs were identified in MCT4 and Sestrin-1 introns, with potentially critical roles in melanoma development.

CONCLUSIONS:

The property of c-MYC, Sestrin-1, and SRPX2 genes to retain specific introns could be clinically used to molecularly differentiate non-melanoma from melanoma tumors.

KEYWORDS:

BCC; SCC; cancer; intron; melanoma; splicing; transcription

PMID:
30795533
PMCID:
PMC6412294
DOI:
10.3390/ijms20040937
[Indexed for MEDLINE]
Free PMC Article

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