Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer

The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from <i>BCL2L12</i>, a member of the BCL2 apoptosis-...

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Main Authors: Paraskevi Karousi, Pinelopi I. Artemaki, Christina D. Sotiropoulou, Spyridon Christodoulou, Andreas Scorilas, Christos K. Kontos
Format: Article
Language:English
Published: MDPI AG 2020-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/21/22/8867
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spelling doaj-f2600d0afedc428989fd54cc7dd0ab942020-11-25T04:11:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-01218867886710.3390/ijms21228867Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal CancerParaskevi Karousi0Pinelopi I. Artemaki1Christina D. Sotiropoulou2Spyridon Christodoulou3Andreas Scorilas4Christos K. Kontos5Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceFourth Surgery Department, University General Hospital “Attikon”, 12462 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, GreeceThe utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from <i>BCL2L12</i>, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two <i>BCL2L12</i> circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel <i>BCL2L12</i> circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel <i>BCL2L12</i> circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.https://www.mdpi.com/1422-0067/21/22/8867circRNAsalternative splicingtranscriptomicsmiRNA spongesRNA-binding proteinsapoptosis
collection DOAJ
language English
format Article
sources DOAJ
author Paraskevi Karousi
Pinelopi I. Artemaki
Christina D. Sotiropoulou
Spyridon Christodoulou
Andreas Scorilas
Christos K. Kontos
spellingShingle Paraskevi Karousi
Pinelopi I. Artemaki
Christina D. Sotiropoulou
Spyridon Christodoulou
Andreas Scorilas
Christos K. Kontos
Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer
International Journal of Molecular Sciences
circRNAs
alternative splicing
transcriptomics
miRNA sponges
RNA-binding proteins
apoptosis
author_facet Paraskevi Karousi
Pinelopi I. Artemaki
Christina D. Sotiropoulou
Spyridon Christodoulou
Andreas Scorilas
Christos K. Kontos
author_sort Paraskevi Karousi
title Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer
title_short Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer
title_full Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer
title_fullStr Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer
title_full_unstemmed Identification of Two Novel Circular RNAs Deriving from <i>BCL2L12</i> and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer
title_sort identification of two novel circular rnas deriving from <i>bcl2l12</i> and investigation of their potential value as a molecular signature in colorectal cancer
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2020-11-01
description The utility of circular RNAs (circRNAs) as molecular biomarkers has recently emerged. However, only a handful of them have already been studied in colorectal cancer (CRC). The purpose of this study was to identify new circRNAs deriving from <i>BCL2L12</i>, a member of the BCL2 apoptosis-related family, and investigate their potential as biomarkers in CRC. Total RNA extracts from CRC cell lines and tissue samples were reversely transcribed. By combining PCR with divergent primers and nested PCR followed by Sanger sequencing, we were able to discover two <i>BCL2L12</i> circRNAs. Subsequently, bioinformatical tools were used to predict the interactions of these circRNAs with microRNAs (miRNAs) and RNA-binding proteins (RBPs). Following a PCR-based pre-amplification, real-time qPCR was carried out for the quantification of each circRNA in CRC samples and cell lines. Biostatistical analysis was used to assess their potential prognostic value in CRC. Both novel <i>BCL2L12</i> circRNAs likely interact with particular miRNAs and RBPs. Interestingly, circ-BCL2L12-2 expression is inversely associated with TNM stage, while circ-BCL2L12-1 overexpression is associated with shorter overall survival in CRC, particularly among TNM stage II patients. Overall, we identified two novel <i>BCL2L12</i> circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.
topic circRNAs
alternative splicing
transcriptomics
miRNA sponges
RNA-binding proteins
apoptosis
url https://www.mdpi.com/1422-0067/21/22/8867
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