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      Circular RNAs: New layer of complexity evading breast cancer heterogeneity

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          Abstract

          Advances in high-throughput sequencing techniques and bioinformatic analysis have refuted the “junk” RNA hypothesis that was claimed against non-coding RNAs (ncRNAs). Circular RNAs (circRNAs); a class of single-stranded covalently closed loop RNA molecules have recently emerged as stable epigenetic regulators. Although the exact regulatory role of circRNAs is still to be clarified, it has been proven that circRNAs could exert their functions by interacting with other ncRNAs or proteins in their own physiologically authentic environment, regulating multiple cellular signaling pathways and other classes of ncRNAs. CircRNAs have also been reported to exhibit a tissue-specific expression and have been associated with the malignant transformation process of several hematological and solid malignancies. Along this line of reasoning, this review aims to highlight the importance of circRNAs in Breast Cancer (BC), which is ranked as the most prevalent malignancy among females. Notwithstanding the substantial efforts to develop a suitable anticancer therapeutic regimen against the heterogenous BC, inter- and intra-tumoral heterogeneity have resulted in an arduous challenge for drug development research, which in turn necessitates the investigation of other markers to be therapeutically targeted. Herein, the potential of circRNAs as possible diagnostic and prognostic biomarkers have been highlighted together with their possible application as novel therapeutic targets.

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

          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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            Molecular portraits of human breast tumours.

            Human breast tumours are diverse in their natural history and in their responsiveness to treatments. Variation in transcriptional programs accounts for much of the biological diversity of human cells and tumours. In each cell, signal transduction and regulatory systems transduce information from the cell's identity to its environmental status, thereby controlling the level of expression of every gene in the genome. Here we have characterized variation in gene expression patterns in a set of 65 surgical specimens of human breast tumours from 42 different individuals, using complementary DNA microarrays representing 8,102 human genes. These patterns provided a distinctive molecular portrait of each tumour. Twenty of the tumours were sampled twice, before and after a 16-week course of doxorubicin chemotherapy, and two tumours were paired with a lymph node metastasis from the same patient. Gene expression patterns in two tumour samples from the same individual were almost always more similar to each other than either was to any other sample. Sets of co-expressed genes were identified for which variation in messenger RNA levels could be related to specific features of physiological variation. The tumours could be classified into subtypes distinguished by pervasive differences in their gene expression patterns.
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              Breast Cancer Treatment

              Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer.
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                Author and article information

                Contributors
                Journal
                Noncoding RNA Res
                Noncoding RNA Res
                Non-coding RNA Research
                KeAi Publishing
                2468-0540
                12 October 2022
                March 2023
                12 October 2022
                : 8
                : 1
                : 60-74
                Affiliations
                [a ]Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
                [b ]Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, 11835, Cairo, Egypt
                [c ]Clinical, Pharmaceutical, and Biological Science Department, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, AL10 9AB, UK
                [d ]Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire hosted By Global Academic Foundation, New Administrative Capital, 11586, Cairo, Egypt
                Author notes
                []Corresponding author. Molecular Genetics Research Team (MGRT), Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire hosted by Global Academic Foundation, New Administrative Capital, 11586, Cairo, Egypt. r.youness@ 123456herts.ac.uk rana.youness21@ 123456gmail.com
                [1]

                Equal Contribution.

                Article
                S2468-0540(22)00056-7
                10.1016/j.ncrna.2022.09.011
                9637558
                36380816
                f40ba89b-540b-4d05-9065-1a94fcda6c16
                © 2022 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 August 2022
                : 4 September 2022
                : 30 September 2022
                Categories
                Article

                circrrnas,breast cancer,diagnosis,prognosis,precision medicine,heterogeneous tumor,biomarkers

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