Prognostic and biological significance of microRNA-221 in breast cancer

Eissa, Sanaa; Matboli, Marwa; Sharawy, Ahmed; El-Sharkawi, Fathia

doi:10.1016/j.gene.2015.08.004

Cited by 20 publications

(20 citation statements)

References 30 publications

(6 reference statements)

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“…This miRNA is known to be an oncogenic miRNA in PC and other cancers as reported by our group and also by other investigators [7,18–21]. In contrast, let-7a was significantly down-regulated in CP and PC plasma samples when compared to HC (Figure 5B) which is consistent with published results, suggesting the global tumor suppressive role of let-7a [22–25].…”

Section: Resultssupporting

confidence: 91%

Differential Expression of Micrornas in Tissues and Plasma Co-exists as a Biomarker for Pancreatic Cancer

et al. 2015

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Objective Pancreatic cancer (PC) is a lethal disease with disappointing results from current treatment modalities, suggesting that novel therapeutic strategies are urgently needed. Since microRNAs (miRNAs) are important player in biology, the clinical utility of miRNAs for designing novel therapeutics is an active area of research. The objective of the present study was to examine differentially expressed miRNAs between normal and tumor tissues, and in plasma samples obtained from PC patients, chronic pancreatitis (CP) patients and healthy subjects (HC). Material and methods The miRNA expression profiling using formalin-fixed paraffin embedded (FFPE) tissues from normal and tumor specimens was accomplished using miRBase version 19 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was subsequently performed in individual samples for 7 selected miRNAs. In addition, qRT-PCR was also performed for assessing the expression of 8 selected miRNAs in plasma samples. Results A significant difference in the expressions of miR-21, miR-205, miR-155, miR-31, miR-203, miR-214 and miR-129-2 were found in tumor tissue samples. Lower expression of miR-214 was found to be associated with better overall survival. We also observed differential expression of 8 miRNAs in plasma samples of CP and PC patients compared to HC. Interestingly, over expression of miR-21, and miR-31 was noted in both tumor tissues and in the plasma. Conclusion We found deregulated expression of miRNAs that could distinguish normal from PC in two different types of samples (tissues and plasma). Interestingly, lower expression of miR-214 was found to be associated with better overall survival. Although not statistically significant, we also observed higher expression of let-7a and lower expression of miR-508 to be associated with overall better survival. We conclude that our study nicely lays the foundation for detailed future investigations for assessing the role of these miRNAs in the pathology of pancreatic cancer.

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Section: Resultssupporting

confidence: 91%

Differential Expression of Micrornas in Tissues and Plasma Co-exists as a Biomarker for Pancreatic Cancer

et al. 2015

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“…It has even been suggested that the direct interaction of miR-221 with ER can cause a phenotypic shift of ER-positive cells to ER-negative more aggressive cells ( Di Leva et al , 2010 ; Riaz et al , 2013 ). Analysis of breast cancer tissue has also confirmed that high miRNA-221 expression correlates with advanced clinical stage and poor prognosis, suggesting its possible role as a biomarker for predicting patient survival ( Eissa et al , 2015 ). Our results suggest that expression of miR-7, miR-339-5p and miR-221-5p may represent a powerful diagnostic tool for predicting metastasis in breast cancer patients.…”

Section: Discussionmentioning

confidence: 98%

MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells

et al. 2017

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Background:MicroRNA-7 (miR-7) has been observed as a potent tumour suppressor in multiple cancer types including breast cancer. The aim of this study was to investigate the response sensitivities of metastatic breast cancer cells to miR-7 and the roles of miR-7 in the interaction of endothelial cells and metastatic cancer cells.Methods:Expression profile of miRNAs in a breast cancer specimen cohort and breast cancer cells were determined using real-time quantitative miRNA assays. Effect of the altering expression of miR-7 on migration, invasion, proliferation, interaction and underlying molecular mechanism of breast cancer cells and endothelial cells was investigated after treatment with the synthesised mimic of miR-7. Luciferase activity analysis was performed to validate Wave-3 as a novel target of miR-7.Results:miR-7 expression was negatively correlated with the stage, grade and survival of the breast cancer patients. There was also differential expression of miRNAs including miR-7 in the breast cancer cells. The synthesised mimic of miR-7 inhibits the motility and wound healing potential of breast cancer cells. The highly metastatic MDA-MB-231 cells are more sensitive to the miR-7 treatment than the poorly invasive MCF-7 cells. Treatment with miR-7 downregulated the expression of EGFR, IGF1R and Wave3 in MDA-MB-231 cells but not in MCF-7 cells. In addition, we further demonstrated that miR-7 inhibited the proliferation, migration and invasion of endothelial cells. And more importantly, miR-7 suppressed the homing and migration of endothelial cells to more aggressive tumour cell conditions.Conclusions:Given the dual inhibitory effect of miR-7 on metastatic breast cancer cells alone and the interaction of endothelial cells with the tumour-conditioned microenvironment, we suggest miR-7 may be a new therapeutic candidate for its capacity not only to prevent breast cancer cell spreading but also to inhibit tumour-associated angiogenesis in the metastatic breast cancer.

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“…In addition, miR-190b was found highly expressed in HR-positive breast cancer tissues and correlated with progression-free survival (PFS) and OS in patients with HR-positive breast cancer [17]. Eissa et al used clinical histology validation, and multivariate survival analysis confirmed that high expression of miR-221 in breast cancer tissue was correlated with the poor prognosis in patients with HR-positive breast cancer [18]. In current report, we identify that low expression levels of miR-891a-5p and miR-383-5p were in metastatic human HR-positive breast tumor tissues ( Figure 1) and contribute to poor DMFS in patients (Figure 2) in our clinical data.…”

Section: Discussionmentioning

confidence: 99%

MiR-891a-5p as a prognostic marker and therapeutic target for hormone receptor-positive breast cancer

Zhang¹,

He²,

Wang³

et al. 2020

J. Cancer

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Background: Breast cancer is one of the most frequent malignant tumors worldwide, with 1.67 million newly-diagnosed cases and 522,000 deaths each year. Therefore, seeking the novel biomarkers and therapeutic targets that contribute to postoperative recurrence and metastasis in patients with breast cancer is emerging and facilitates the development of innovative therapeutics. Methods: Retrieving the dataset of patients with hormone receptor (HR)-positive breast cancers from Gene Expression Omnibus (GEO) and collecting the data from the patients with HR-positive breast cancers enrolled in the First Affiliated Hospital of China Medical University are so as to identify the miRNAs associated with metastasis and distant metastasis-free survival (DMFS). Then MTT and Transwell migration assays were used to validate the effect of miRNAs on cell proliferation and migration of estrogen receptor-positive breast cancer T47D and MCF7 cells in vitro, respectively. Results: From GSE59829 dataset, the miRNA expression levels of miR-891a-5p, miR-383-5p and miR-1295a were significantly downregulated while the levels of miR-128-3p, miR-661 and miR-296-3p were significantly upregulated in breast cancers from patients with metastasis as compared to the matched non-metastatic group. Moreover, low expression levels of miR-891a-5p, miR-383-5p and miR-1295a or high expression levels of miR-128-3p, miR-661 and miR-296-3p were respectively associated with low DMFS in patients with breast cancer. Our clinical cohort study supported that the levels of miR-891a-5p, miR-383-5p and miR-1295a were significantly lower in breast cancers from the metastasis group when compared with non-metastatic group. However, there is no significant difference with regard to the levels of miR-128-3p, miR-661 and miR-296-3p in breast cancer between these two groups. Moreover, low expression levels of miR-891a-5p and miR-383-5p but not miR-1295a in breast cancer were significantly associated with low DMFS in patients, implying that the expression of miR-891a-5p and miR-383-5p were the potential prognosis markers for metastatic human breast cancers. Further investigation disclosed that miR-891a-5p but not miR-383-5p restrained both proliferation and migration of T47D and MCF7 cells. In silico analysis of miRNAs target gene through online computational algorithms revealed that A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is the downstream target for miR-891a-5p. Further study confirmed that miR-891a-5p impeded ADAM10 expression by directly binding to its 3'UTR, leading to the inhibition of breast cancer cells proliferation and migration. Moreover, silencing ADAM10 inhibited T47D and MCF7 cells growth and migration. Conclusion: miR-891a-5p is the vital prognostic marker for HR-positive breast cancer. In addition, miR-891a-5p and miR-383-5p are the potential targets for HR-positive breast cancer therapeutics.

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Prognostic and biological significance of microRNA-221 in breast cancer

Cited by 20 publications

References 30 publications

Differential Expression of Micrornas in Tissues and Plasma Co-exists as a Biomarker for Pancreatic Cancer

Differential Expression of Micrornas in Tissues and Plasma Co-exists as a Biomarker for Pancreatic Cancer

MicroRNA-7 suppresses the homing and migration potential of human endothelial cells to highly metastatic human breast cancer cells

MiR-891a-5p as a prognostic marker and therapeutic target for hormone receptor-positive breast cancer

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