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Article

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

1
Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, 15701 Athens, Greece
2
Fourth Surgery Department, University General Hospital “Attikon”, 12462 Athens, Greece
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(22), 8867; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228867
Received: 26 October 2020 / Revised: 6 November 2020 / Accepted: 15 November 2020 / Published: 23 November 2020
(This article belongs to the Special Issue Molecular Biomarkers in Colorectal Adenocarcinoma)
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 BCL2L12, 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 BCL2L12 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 BCL2L12 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 BCL2L12 circRNAs, one of which can further stratify TNM stage II patients into two subgroups with substantially distinct prognosis.
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Keywords: circRNAs; alternative splicing; transcriptomics; miRNA sponges; RNA-binding proteins; apoptosis; colon adenocarcinoma; tumor biomarker; CRC prognosis; TNM stage circRNAs; alternative splicing; transcriptomics; miRNA sponges; RNA-binding proteins; apoptosis; colon adenocarcinoma; tumor biomarker; CRC prognosis; TNM stage
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MDPI and ACS Style

Karousi, P.; Artemaki, P.I.; Sotiropoulou, C.D.; Christodoulou, S.; Scorilas, A.; Kontos, C.K. Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer. Int. J. Mol. Sci. 2020, 21, 8867. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228867

AMA Style

Karousi P, Artemaki PI, Sotiropoulou CD, Christodoulou S, Scorilas A, Kontos CK. Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer. International Journal of Molecular Sciences. 2020; 21(22):8867. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228867

Chicago/Turabian Style

Karousi, Paraskevi, Pinelopi I. Artemaki, Christina D. Sotiropoulou, Spyridon Christodoulou, Andreas Scorilas, and Christos K. Kontos. 2020. "Identification of Two Novel Circular RNAs Deriving from BCL2L12 and Investigation of Their Potential Value as a Molecular Signature in Colorectal Cancer" International Journal of Molecular Sciences 21, no. 22: 8867. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228867

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