Molecular mechanisms of circular RNA in breast cancer: a narrative review

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Abstract

Background and Objective

Breast cancer is presently the most prevalent cancer and the leading cause of cancer-related deaths in women worldwide. Circular RNA (circRNA) is a class of closed circRNAs lacking a 5'-end cap structure and a 3'-end polyA tail, which is highly stable and widely involved in a variety of pathophysiological processes such as cell proliferation, differentiation, and apoptosis. In recent years, accumulating studies have shown that circRNAs play an important role in the development and prognosis of breast cancer, but there are fewer literature reviews on their intrinsic molecular mechanisms which is the aim of this study.

Methods

This review synthesizes the findings of literature retrieved from searches of PubMed and Google Scholar databases, hand searches, and authoritative texts. Citations mainly originate from the past 3 years. The articles need to describe the role of circRNA in breast cancer; no language restrictions were imposed.

Key Content and Findings

This review summarizes the latest relevant literature and systematically reviews the four main mechanisms of circRNA in breast cancer from the perspective of circRNA function. At the same time, we describe the formation mechanism, characterization, and biological functions of circRNAs.

Conclusions

We reviewed the status of actual knowledge about circRNA biogenesis and functions and summarized novel findings regarding the molecular mechanism of circRNA in breast cancer. Meanwhile, this review explores the possibility of circRNAs for becoming new biodiagnostic indicators and therapeutic targets in breast cancer.

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Most cited references 58

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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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Cancer statistics, 2022

Rebecca Siegel, Kimberly D Miller, Hannah Fuchs … (2022)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.

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Circular RNAs are abundant, conserved, and associated with ALU repeats.

W. R. Jeck, J A Sorrentino, K. Wang … (2013)

Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a "backsplice") and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression.

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Author and article information

Journal

Journal ID (nlm-ta): Transl Cancer Res

Journal ID (iso-abbrev): Transl Cancer Res

Journal ID (publisher-id): TCR

Title: Translational Cancer Research

Publisher: AME Publishing Company

ISSN (Print): 2218-676X

ISSN (Electronic): 2219-6803

Publication date (Electronic): 26 February 2024

Publication date (Print): 29 February 2024

Volume: 13

Issue: 2

Pages: 1139-1149

Affiliations

[1]deptDepartment of Thyroid and Breast Surgery , The Affiliated Hospital of Inner Mongolia Medical University , Hohhot, China

Author notes

Contributions: (I) Conception and design: Z Li, R Zhang; (II) Administrative support: R Zhang, D Li; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: Z Li, R Guo; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Correspondence to: Rui Zhang, MD. Department of Thyroid and Breast Surgery, The Affiliated Hospital of Inner Mongolia Medical University, No. 1 North Channel Road, Huimin District, Hohhot 010010, China. Email: zhangrui999999@ 123456163.com .

[^]

ORCID: 0009-0007-3452-5920.

Article

Publisher ID: tcr-13-02-1139

DOI: 10.21037/tcr-23-1760

PMC ID: 10928600

PubMed ID: 38482408

SO-VID: e8dca013-1605-4170-a33b-3cf0e10e2be3

License:

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

History

Date received : 22 September 2023

Date accepted : 28 December 2023

Funding

Funded by: the Inner Mongolia Autonomous Region Natural Science Foundation Project

Award ID: No. 2022MS08010

Funded by: the Inner Mongolia Autonomous Region Science and Technology Programme

Award ID: No. 2023YFSH0039

Molecular mechanisms of circular RNA in breast cancer: a narrative review

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Abstract

Background and Objective

Methods

Key Content and Findings

Conclusions

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Karger: Oncology

Most cited references 58

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

Cancer statistics, 2022

Circular RNAs are abundant, conserved, and associated with ALU repeats.

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