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      The Emerging Roles of Exosomal miRNAs in Breast Cancer Progression and Potential Clinical Applications

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          Abstract

          Breast cancer remains the leading malignancy in terms of morbidity and mortality today. The tumor microenvironment of breast cancer includes multiple cell types, secreted proteins, and signaling components such as exosomes. Among these, exosomes have a lipid bilayer structure. Exosomes can reflect the biological traits of the parent cell and carry a variety of biologically active components, including proteins, lipids, small molecules, and non-coding RNAs, which include miRNA, lncRNA, and circRNA. MiRNAs are a group of non-coding RNAs of approximately 20–23 nucleotides in length encoded by the genome, triggering silencing and functional repression of target genes. MiRNAs have been shown to play a significant role in the development of cancer owing to their role in the prognosis, pathogenesis, diagnosis, and treatment of cancer. MiRNAs in exosomes can serve as effective mediators of information transfer from parental cells to recipient cells and trigger changes in biological traits such as proliferation, invasion, migration, and drug resistance. These changes can profoundly alter the progression of breast cancer. Therefore, here, we systematically summarize the association of exosomal miRNAs on breast cancer progression, diagnosis, and treatment in the hope of providing novel strategies and directions for subsequent breast cancer treatment.

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          The biology, function, and biomedical applications of exosomes

          The study of extracellular vesicles (EVs) has the potential to identify unknown cellular and molecular mechanisms in intercellular communication and in organ homeostasis and disease. Exosomes, with an average diameter of ~100 nanometers, are a subset of EVs. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate the final content of the exosomes. Their diverse constituents include nucleic acids, proteins, lipids, amino acids, and metabolites, which can reflect their cell of origin. In various diseases, exosomes offer a window into altered cellular or tissue states, and their detection in biological fluids potentially offers a multicomponent diagnostic readout. The efficient exchange of cellular components through exosomes can inform their applied use in designing exosome-based therapeutics.
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            Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020

            Background: Cancer is one of the leading causes of death globally, but its burden is not uniform. GLOBOCAN 2020 has newly updated the estimates of cancer burden. This study summarizes the most recent changing profiles of cancer burden worldwide and in China and compares the cancer data of China with those of other regions. Methods: We conducted a descriptive secondary analysis of the GLOBOCAN 2020 data. To depict the changing global profile of the leading cancer types in 2020 compared with 2018, we extracted the numbers of cases and deaths in 2018 from GLOBOCAN 2018. We also obtained cancer incidence and mortality from the 2015 National Cancer Registry Report in China when sorting the leading cancer types by new cases and deaths. For the leading cancer types according to sex in China, we summarized the estimated numbers of incidence and mortality, and calculated China's percentage of the global new cases and deaths. Results: Breast cancer displaced lung cancer to become the most leading diagnosed cancer worldwide in 2020. Lung, liver, stomach, breast, and colon cancers were the top five leading causes of cancer-related death, among which liver cancer changed from the third-highest cancer mortality in 2018 to the second-highest in 2020. China accounted for 24% of newly diagnosed cases and 30% of the cancer-related deaths worldwide in 2020. Among the 185 countries included in the database, China's age-standardized incidence rate (204.8 per 100,000) ranked 65th and the age-standardized mortality rate (129.4 per 100,000) ranked 13th. The two rates were above the global average. Lung cancer remained the most common cancer type and the leading cause of cancer death in China. However, breast cancer became the most frequent cancer type among women if the incidence was stratified by sex. Incidences of colorectal cancer and breast cancer increased rapidly. The leading causes of cancer death varied minimally in ranking from 2015 to 2020 in China. Gastrointestinal cancers, including stomach, colorectal, liver, and esophageal cancers, contributed to a massive burden of cancer for both sexes. Conclusions: The burden of breast cancer is increasing globally. China is undergoing cancer transition with an increasing burden of lung cancer, gastrointestinal cancer, and breast cancers. The mortality rate of cancer in China is high. Comprehensive strategies are urgently needed to target China's changing profiles of the cancer burden.
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              Breast cancer

              Breast cancer is still the most common cancer worldwide. But the way breast cancer is viewed has changed drastically since its molecular hallmarks were extensively characterised, now including immunohistochemical markers (eg, ER, PR, HER2 [ERBB2], and proliferation marker protein Ki-67 [MKI67]), genomic markers (eg, BRCA1, BRCA2, and PIK3CA), and immunomarkers (eg, tumour-infiltrating lymphocytes and PD-L1). New biomarker combinations are the basis for increasingly complex diagnostic algorithms. Neoadjuvant combination therapy, often including targeted agents, is a standard of care (especially in HER2-positive and triple-negative breast cancer), and the basis for de-escalation of surgery in the breast and axilla and for risk-adapted post-neoadjuvant strategies. Radiotherapy remains an important cornerstone of breast cancer therapy, but de-escalation schemes have become the standard of care. ER-positive tumours are treated with 5-10 years of endocrine therapy and chemotherapy, based on an individual risk assessment. For metastatic breast cancer, standard therapy options include targeted approaches such as CDK4 and CDK6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PD-L1 immunotherapy, depending on tumour type and molecular profile. This range of treatment options reflects the complexity of breast cancer therapy today.
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                Author and article information

                Journal
                Breast Cancer (Dove Med Press)
                Breast Cancer (Dove Med Press)
                bctt
                Breast Cancer : Targets and Therapy
                Dove
                1179-1314
                16 November 2023
                2023
                : 15
                : 825-840
                Affiliations
                [1 ]Department of Thyroid and Breast Surgery, Shenzhen Qianhai Shekou Free Trade Zone Hospital , Shenzhen, 518067, People’s Republic of China
                [2 ]Department of Nephrology, Renmin Hospital of Wuhan University , Wuhan, 430060, People’s Republic of China
                [3 ]Department of Pediatrics, Dalian Municipal Women and Children’s Medical Center (Group), Dalian Medical University , Dalian, Liaoning Province, 116011, People’s Republic of China
                [4 ]Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei Province, 430030, People’s Republic of China
                Author notes
                Correspondence: Shengxuan Liu, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei Province, 430030, People’s Republic of China, Tel +86 133 8756 1016, Email tongjishengxuanl@163.com
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0009-0007-2808-2182
                http://orcid.org/0009-0002-1629-2178
                http://orcid.org/0009-0009-7203-5548
                Article
                432750
                10.2147/BCTT.S432750
                10658810
                d4de0149-8c0e-41ad-b9f2-4a3b8095f293
                © 2023 Li et al.

                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
                : 13 September 2023
                : 08 November 2023
                Page count
                Figures: 2, Tables: 1, References: 107, Pages: 16
                Funding
                Funded by: Nature Science Foundation of Hubei Province;
                This work was supported by Nature Science Foundation of Hubei Province (2020CFB685).
                Categories
                Review

                breast cancer,tumor microenvironment,exosome,mirnas,detection,therapy

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