Circulating microRNAs - a new horizon in molecular diagnosis of breast cancer

Hagrass, Hoda A.; Sharaf, Samar M.; Pasha, Heba F.; Tantawy, Enas A.; Mohamed, Randa H.; Kassem, Rasha

doi:10.18632/genesandcancer.66

Cited by 47 publications

(44 citation statements)

References 29 publications

(40 reference statements)

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“…A number of previous studies have indicated that miRNAs, being one of the main functional components of exosome cargo, may play a crucial role in cell-to-cell communication and eventually regulate the biological functions of recipient cells. It is known that miR-92a and miR-25-3p are up-regulated in cell lines with enhanced EMT, cell motility, and angiogenesis [ 25 , 26 , 27 , 28 , 29 , 30 ]. Since the miR-16-5p expression was stable and reproducible, it was chosen as an endogenous control to normalize the miRNA expression [ 30 , 31 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

Konoshenko

Sagaradze

Orlova

et al. 2020

IJMS

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Exosomes are crucial players in cell-to-cell communication and are involved in tumorigenesis. There are two fractions of blood circulating exosomes: free and cell-surface-associated. Here, we compared the effect of total blood exosomes (contain plasma exosomes and blood cell-surface-associated exosomes) and plasma exosomes from breast cancer patients (BCPs, n = 43) and healthy females (HFs, n = 35) on crucial steps of tumor progression. Exosomes were isolated by ultrafiltration, followed by ultracentrifugation, and characterized by cryo-electron microscopy (cryo-EM), nanoparticle tracking analysis, and flow cytometry. Cryo-EM revealed a wider spectrum of exosome morphology with lipid bilayers and vesicular internal structures in the HF total blood in comparison with plasma. No differences in the morphology of both exosomes fractions were detected in BCP blood. The plasma exosomes and total blood exosomes of BCPs had different expression levels of tumor-associated miR-92a and miR-25-3p, induced angiogenesis and epithelial-to-mesenchymal transition (EMT), and increased the number of migrating pseudo-normal breast cells and the total migration path length of cancer cells. The multidirectional effects of HF total blood exosomes on tumor dissemination were revealed; they suppress the angiogenesis and total migration path length of MCF10A, but stimulate EMT and increase the number of migrating MCF10A and the total path length of SKBR3 cells. In addition, HF plasma exosomes enhance the metastasis-promoting properties of SKBR3 cells and stimulate angiogenesis. Both cell-free and blood cell-surface-associated exosomes are involved in the crucial stages of carcinogenesis: the initiation of EMT and the stimulation of proliferation, cell migration, and angiogenesis. Thus, for the estimation of the diagnostic/prognostic significance of circulating exosomes in the blood of cancer patients more correctly, the total blood exosomes, which consist of plasma exosomes and blood cell-surface-associated exosomes should be used.

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Section: Resultsmentioning

confidence: 99%

Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

Konoshenko

Sagaradze

Orlova

et al. 2020

IJMS

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“…Specific circulating miRNAs are useful markers for the diagnosis, therapy evaluation and prognosis of breast cancer. 35 , 36 , 37 miRNAs show different patterns of expression in the serum of breast cancer patients depending on their family subtypes or type of cancers. 38 For example, Das et al 39 reported that the level of miR-720 was relatively high in the serum of both primary and metastatic breast cancer patients.…”

Section: Discussionmentioning

confidence: 99%

miR-200b inhibits proliferation and metastasis of breast cancer by targeting fucosyltransferase IV and α1,3-fucosylated glycans

et al. 2017

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Aberrant protein fucosylation is associated with cancer malignancy. Fucosyltransferase IV (FUT4) is the key enzyme catalyzing the biosynthesis of α1,3-linkage fucosylated glycans carried by glycoproteins on the cell surface, such as the tumor-associated sugar antigen Lewis Y (LeY). An abnormal increase in the levels of FUT4 and LeY is observed in many cancers and correlated with cell proliferation and metastasis. Some microRNAs (miRNAs) are known to negatively regulate gene expression. FUT4 is an oncogenic glycogene, and thus it is important to identify the specific miRNA targeting FUT4. In current study, we first identified miR-200b as a specific miRNA that inhibited FUT4 expression. We found that miR-200b level was decreased, whereas that of FUT4 was increased in tissues and serum of breast cancer compared with that in the control by real-time PCR, western blotting and enzyme-linked immunosorbent assay. The alterations of miR-200b and FUT4 level were recovered after chemotherapy. The results also showed that miR-200b suppressed FUT4 expression and inhibited tumor growth and metastasis in MCF-7 and MDA-MB-231 breast cancer cells, as well as in the xenografted tumor tissues and metastatic lung tissues. miR-200b decreased the α1,3-fucosylation and LeY biosynthesis on epidermal growth factor receptor (EGFR), as well as inactivation of EGFR and downstream phosphoinositide-3 kinase/Akt signaling pathway. In conclusion, the study highlights that FUT4 could apply as a novel target for miR-200b that suppress the proliferation and metastasis of breast cancer cells by reducing α1,3-fucosylation and LeY biosynthesis of glycoproteins. miR-200b and FUT4 are potential diagnostic and therapeutic targets for breast cancer.

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“…Breast cancer (BC) represents the second most prevalent type of tumor with the highest mortality rate in the world among women. Annually, more than one million women are diagnosed with breast cancer and > 400,000 die from this disease [1]. The evolution of this neoplasm occurs when the cells break off and spread to other regions of the body [2].…”

Section: Introductionmentioning

confidence: 99%

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

et al. 2018

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Circulating microRNAs - a new horizon in molecular diagnosis of breast cancer

Cited by 47 publications

References 29 publications

Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

Total Blood Exosomes in Breast Cancer: Potential Role in Crucial Steps of Tumorigenesis

miR-200b inhibits proliferation and metastasis of breast cancer by targeting fucosyltransferase IV and α1,3-fucosylated glycans

Melatonin restrains angiogenic factors in triple-negative breast cancer by targeting miR-152-3p: In vivo and in vitro studies

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