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      Biogenesis, Functions, and Role of CircRNAs in Lung Cancer

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          Abstract

          CircRNAs, a class of endogenous non-coding RNAs with closed-loop structures, have attracted increasing attention because of their good stability, high specificity of tissue expression, long half-life, and highly conserved sequence. CircRNAs have multiple biological functions, including miRNA sponge, transcription regulator, protein translation, interaction with protein, RNA maturation, and so on. These functions indicate the important role of circRNAs in tumorigenesis and malignant progression and their potential as potent diagnostic biomarkers and therapeutic molecules. In recent years, an increasing body of evidence suggests that circRNAs play a crucial role in proliferation, migration, invasion, and apoptosis of lung cancer cells. Therefore, circRNAs have gradually become a research focus in the diagnosis and treatment of lung cancer patients. This review summarizes the classification, biogenesis, and function of circRNAs, and discusses the role of circRNAs in the diagnosis, prognosis, and treatment of lung cancer patients.

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          Most cited references158

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Circular RNAs are a large class of animal RNAs with regulatory potency.

            Sebastian Memczak, Marvin Jens, Antigoni Elefsinioti … (2013)
            Circular RNAs (circRNAs) in animals are an enigmatic class of RNA with unknown function. To explore circRNAs systematically, we sequenced and computationally analysed human, mouse and nematode RNA. We detected thousands of well-expressed, stable circRNAs, often showing tissue/developmental-stage-specific expression. Sequence analysis indicated important regulatory functions for circRNAs. We found that a human circRNA, antisense to the cerebellar degeneration-related protein 1 transcript (CDR1as), is densely bound by microRNA (miRNA) effector complexes and harbours 63 conserved binding sites for the ancient miRNA miR-7. Further analyses indicated that CDR1as functions to bind miR-7 in neuronal tissues. Human CDR1as expression in zebrafish impaired midbrain development, similar to knocking down miR-7, suggesting that CDR1as is a miRNA antagonist with a miRNA-binding capacity ten times higher than any other known transcript. Together, our data provide evidence that circRNAs form a large class of post-transcriptional regulators. Numerous circRNAs form by head-to-tail splicing of exons, suggesting previously unrecognized regulatory potential of coding sequences.
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              Natural RNA circles function as efficient microRNA sponges.

              Thomas B. Hansen, Trine I. Jensen, Bettina H. Clausen … (2014)
              MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more than 70 selectively conserved miRNA target sites, and it is highly and widely associated with Argonaute (AGO) proteins in a miR-7-dependent manner. Although the circRNA is completely resistant to miRNA-mediated target destabilization, it strongly suppresses miR-7 activity, resulting in increased levels of miR-7 targets. In the mouse brain, we observe overlapping co-expression of ciRS-7 and miR-7, particularly in neocortical and hippocampal neurons, suggesting a high degree of endogenous interaction. We further show that the testis-specific circRNA, sex-determining region Y (Sry), serves as a miR-138 sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA.
              Article 0 comments Cited 2127 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cancer Manag Res
                Journal ID (iso-abbrev): Cancer Manag Res
                Journal ID (publisher-id): cmar
                Journal ID (pmc): cancmanres
                Title: Cancer Management and Research
                Publisher: Dove
                ISSN (Electronic): 1179-1322
                Publication date (Electronic): 24 August 2021
                Publication date Collection: 2021
                Volume: 13
                Pages: 6651-6671
                Affiliations
                [1 ]Department of Clinical Laboratory, Harbin Medical University Cancer Hospital , Harbin, 150081, People’s Republic of China
                Author notes
                Correspondence: Hui Xu Email xuhui@hrbmu.edu.cn
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0002-7596-8011
                Article
                Publisher ID: 324812
                DOI: 10.2147/CMAR.S324812
                PMC ID: 8403226
                PubMed ID: 34466035
                SO-VID: 3db6e2dc-8197-4f2f-ac42-baff9c9c3671
                Copyright © © 2021 Dong et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 21 June 2021
                Date accepted : 09 August 2021
                Page count
                Figures: 2, Tables: 10, References: 158, Pages: 21
                Funding
                Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;
                Funded by: Haiyan Foundation from Harbin Medical University Cancer Hospita;
                This publication was supported by the National Natural Science Foundation of China (No.31600662) and Haiyan Foundation from Harbin Medical University Cancer Hospital (No. JJMS2020-02) to H.X.
                Categories
                Subject: Review

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circrna,lung cancer,diagnosis,prognosis,treatment
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: circrna, lung cancer, diagnosis, prognosis, treatment

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