MicroRNAs and Metastasis-related Gene Expression in Egyptian Breast Cancer Patients

Collage of Pharmacy, Pharmacology Department, King Saud University, Riyadh, Saudi Arabia.
Asian Pacific journal of cancer prevention: APJCP (Impact Factor: 2.51). 02/2012; 13(2):591-8. DOI: 10.7314/APJCP.2012.13.2.591
Source: PubMed


MicroRNAs (miRNAs) are a class of naturally occurring small noncoding RNAs that regulate gene expression, cell growth, differentiation and apoptosis by targeting mRNAs for translational repression or cleavage. The present study was conducted to study miRNAs in Egyptian breast cancer (BC) and their relation to metastasis, tumor invasion and apoptosis in addition to their association with the ER and PR statuses.
Real Time RT-PCR was performed to identify the miRNA expression level of eight miRNAs and eight metastatic-related genes in 40 breast cancer samples and their adjacent non-neoplastic tissues. The expression levels of each miRNA relative to U6 RNA were determined. Also, miRNA expression profiles of the BC and their corresponding ANT were evaluated.
The BC patients showed an up-regulation in miRNAs (mir-155, mir-10, mir-21 and mir-373) with an upregulation in MMP2, MMp9 and VEGF genes. We found down regulation in mir-17p, mir-126, mir-335, mir-30b and also TIMP3, TMP1 and PDCD4 genes in the cancer tissue compared to the adjacent non-neoplastic tissues. Mir -10b, mir -21, mir-155 and mir373 and the metastatic genes MMP2, MMP9 and VEGF were significantly associated with an increase in tumor size (P<0.05). No significant difference was observed between any of the studied miRNAs regarding lymph node metastasis. Mir-21 was significantly over-expressed in ER-/PR- cases.
Specific miRNAs (mir-10, mir-21, mir-155, mir-373, mir-30b, mir-126, mir-17p, mir-335) are associated with tumor metastasis and other clinical characteristics for BC, facilitating identification of individuals who are at risk.

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Available from: Abdel-Rahamn Zekri, Dec 16, 2013
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    • "Another five were excluded due to data that were incomplete or inappropriately calculated or original data that could not be obtained despite attempts to contact the authors. Therefore, 15 [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] articles were considered in the present meta-analysis. Among them, 13 discussed the different expression level of miR-155 between breast cancer samples and normal samples, and another 2 only discussed it between different subtype breast cancers. "
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    ABSTRACT: Objective: Previous studies demonstrated that the associations between expression level of microRNA-155 (miR-155) and clinicopathological significance of breast cancer remained inconsistent. Therefore, we performed a meta-analysis based on eligible studies to summarize the possible associations. Methods: We identified eligible studies published up to May 2014 by a comprehensive search of PubMed, EMBASE, CNKI, and VIP databases. The analysis was performed with RevMan. 5.0 software. Results: A total of 15 studies were included. The results of meta-analysis showed that miR-155 was positively correlated with breast cancer with standardized mean difference (SMD) = 1.22. Elevated miR-155 was found in Her-2 positive or lymph node metastasis positive, or p53 mutant type breast cancer. But the result showed to be insignificant in TNM comparison. With respect to estrogen receptor alpha (ER) and progesterone receptor (PR) status, both of them showed significant associations with SMD = -1.2 and -1.85, respectively. Conclusion: MiR-155 detection might have a diagnostic value in breast cancer patients. It might be used as an auxiliary biomarker for different clinicopathological breast cancer.
    Full-text · Article · Aug 2014 · BioMed Research International
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    • "cancer in vitro and in vivo. Using the result of Hafez's research (Hafez et al., 2012) for reference that the breast cancer patients showed an up-regulation in RNAs with an upregulation in MMP2 and MMP-9 genes, we also investigated the expression of the invasion associating factors, MMP-2 and MMP-9. Therefore, the role of LOX in the invasion of breast cancer was studied. "
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    ABSTRACT: Objective: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion and metastasis of breast cancer cells by RNA interference. Methods: LOX-RNAi-LV was designed, synthesized, and then transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 was determined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasiveness were assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normal breast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry. Results: Expression of LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lower in the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231 cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer, cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20), respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2, but not age. LOX protein was positively correlated with MMP-2 and MMP-9. Conclusion: LOX displayed an important role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression which probably exerted synergistic effects on the extracellular matrix (ECM).
    Preview · Article · Jul 2012 · Asian Pacific journal of cancer prevention: APJCP
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    ABSTRACT: The discovery that microRNA (miRNA) regulates metastasis provide a principal molecular basis for tumor heterogeneity. A characteristic of solid tumors is their heterogenous distribution of blood vessels, with significant hypoxia occurring in regions (centers of tumor) of low blood flow. It is necessary to discover the mechanism of breast cancer metastasis in relation to the fact that there is a differential distribution of crucial microRNA in tumors from centers to edges. Breast tissues from 48 patients (32 patients with breast cancer) were classified into the high invasive and metastatic group (HIMG), low invasive and metastatic group (LIMG), and normal group. Samples were collected from both the centers and edges of all tumors. The first six specimens were detected by microRNA array, and the second ten specimens were detected by real-time qRT- PCR and Western blot analyses. Correlation analysis was performed between the miRNAs and target proteins. The relative content of miR-20a and miR-20b was lower in the center of the tumor than at the edge in the LIMG, lower at the edge of the tumor than in the center in the HIMG, and lower in breast cancer tissues than in normal tissues. VEGF-A and HIF-1alpha mRNA levels were higher in the HIMG than in the LIMG, and levels were higher in both groups than in the normal group; there was no difference in mRNA levels between the edge and center of the tumor. VEGF-A and HIF-1alpha protein levels were higher in the HIMG than in the LIMG, and protein levels in both groups were higher than in the normal group; there was a significant difference in protein expression between the edge and center of the tumor. Correlation analysis showed that the key miRNAs (miR-20a and miR-20b) negatively correlated with the target proteins (VEGF-A and HIF-1alpha). Our data suggest that miR-20a and miR-20b are differentially distributed in breast cancer, while VEGF-A and HIF-1alpha mRNA had coincident distributions, and VEGF-A and HIF-1alpha proteins had uneven and opposing distributions to the miRNAs. It appears that one of the most important facets underlying metastatic heterogeneity is the differential distribution of miR-20a and miR-20b and their regulation of target proteins.
    Preview · Article · May 2012 · Asian Pacific journal of cancer prevention: APJCP
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