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Comprehensive analysis of circular RNAs in pathological states: biogenesis, cellular regulation, and therapeutic relevance

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Abstract

Circular RNAs (circRNAs) are members of the non-coding transcriptome; however, some of them are translated into proteins. These transcripts have important roles in both physiological and pathological mechanisms due to their ability to directly influence cellular signaling pathways. Specifically, circRNAs are regulators of transcription, translation, protein interaction, and signal transduction. An increased knowledge within their area is observed over the last few years, concomitant with the development of next-generation sequencing techniques. circRNAs are mostly tissue and disease specific with the ability of specifically changing the biological behavior of cells. The altered expression profile is currently investigated as novel minimally invasive diagnosis/prognosis tool and also therapeutic target in human disease. The diagnosis approach is based on their level modification within pathological states, especially cancer, where circRNAs’ therapies are intensively explored in anti-aging strategies, diabetes, cardiovascular diseases, and malignant pathologies, and are relying on the restoration of homeostatic profiles.

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Abbreviations

Ago2:

Argonaute 2

circRNAs:

Circular RNAs

EGFR:

Epidermal growth factor receptor

ElcircRNA:

Exon–intron circular RNA

EMT:

Epithelial-to-mesenchymal transition

fcircRNA:

Fusogenic circRNA

lncRNAs:

Long non-coding RNAs

m6A:

N6-Methyladenosine

miRNAs:

MicroRNAs

ncRNAs:

Non-coding RNAs

siRNAs:

Small interfering RNAs

tricRNAs:

tRNA intronic circular RNAs

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Funding

This work was supported by a POC Grant, entitled “Clinical and economical impact of personalized targeted anti-microRNA therapies in reconverting lung cancer chemoresistance”-CANTEMIR (project no. 35/01.09.2016, Cod MySMIS 103375) and by PN-III-P1-1.2-PCCDI-2017-0737 (“Genomic mapping of population from polluted area with radioactivity and heavy metals to increase national security-ARTEMIS and PN-III-P2-2.1-PED-2016-0425 (project no 178 PED).

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Authors and Affiliations

  1. Research Center for Functional Genomics, Biomedicine and Translational Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania

    Cornelia Braicu & Ioana Berindan-Neagoe

  2. MEDFUTURE-Research Center for Advanced Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 23 Marinescu Street, 400337, Cluj-Napoca, Romania

    Andreea-Alina Zimta, Diana Gulei & Ioana Berindan-Neagoe

  3. Nordlogic Software, 10-12, Rene Descartes Street, 400486, Cluj-Napoca, Romania

    Andrei Olariu

  4. Department of Functional Genomics and Experimental Pathology, “Prof. Dr. Ion Chiricuta” The Oncology Institute, 34-36 Republicii Street, 400015, Cluj-Napoca, Romania

    Ioana Berindan-Neagoe

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  1. Cornelia Braicu
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  2. Andreea-Alina Zimta
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  3. Diana Gulei
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  4. Andrei Olariu
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  5. Ioana Berindan-Neagoe
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Contributions

CB wrote the paper; A-AZ participated for the introduction part and for figures concept; DG assisted for the table preparation and wrote the final part related to the circulating cirRNAs as biomarkers. AO was responsible for the figure design and for the part related to data-based and programs for circRNAs application. IBN was the design of the study, final correction of the manuscript. All the authors assisted in the preparation of the manuscript and editing and approved the final version of the manuscript.

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Correspondence to Cornelia Braicu or Ioana Berindan-Neagoe.

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Braicu, C., Zimta, AA., Gulei, D. et al. Comprehensive analysis of circular RNAs in pathological states: biogenesis, cellular regulation, and therapeutic relevance. Cell. Mol. Life Sci. 76, 1559–1577 (2019). https://doi.org/10.1007/s00018-019-03016-5

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