A summary for molecular regulations of miRNAs in breast cancer

Yahya, Shaymaa M. M.; Elsayed, Ghada H.

doi:10.1016/j.clinbiochem.2014.12.013

Cited by 39 publications

(37 citation statements)

References 147 publications

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“…It is the leading cause of cancer death in less-developed countries (Majeed et al, 2014;Carter, 2014). Because up to 10% of the total number of women diagnosed with breast cancer report a family history of the disease, microRNAs (miRNAs) may represent a promising new class of potential susceptibility genes (Harquail et al, 2012;Yahya and Elsayed, 2015).…”

Section: Introductionmentioning

confidence: 99%

Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population

Qi¹,

Wang²,

Zhou³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Single-nucleotide polymorphisms in microRNAs (miRNAs) may dramatically affect gene expression and subsequently alter individual susceptibility to cancer, and thus has become a research hotspot for many cancer types, including breast cancer. We recruited 321 breast cancer patients and 290 controls in our study. Four established miRNA single-nucleotide polymorphisms (mir-499 rs3746444 A>G; miR-27a rs895819 A>G; miR-196a2 rs11614913 T>C; miR-146a rs2910164 G/C) were detected using Taqman assays. Mature miRNA expression, allele distribution, and the association with clinical features were further analyzed. Our results showed that the miR146a rs2910164 G/C polymorphism was associated with an elevated risk of breast cancer (odds ratio = 1.85, 95% confidence interval = 1.03-3.32; P < 0.05). Compared with the ancestral T allele in miR-196a2 rs11614913, the variant C allele was consistently associated with an increased risk of breast cancer (odds ratio = 2.20, 95% confidence interval = 1.19-4.09, P < 0.01) and clinical pathological type (P < 0.01). miR-27a rs895819 A>G and miR-499 rs3746444 A>G were not associated with breast cancer risk. Analysis of mature miRNA expression confirmed that the variant C allele in miR146a rs2910164 and miR-196a2 rs11614913 dramatically inhibited production of their mature products. Our results suggested that miR-146a rs2910164 G>C and miR-196a2 rs11614913 T>C may be biomarkers for predicting breast cancer risk in the Chinese population.

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Section: Introductionmentioning

confidence: 99%

Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population

Qi¹,

Wang²,

Zhou³

et al. 2015

Genet. Mol. Res.

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“…In addition, inactivation by detoxification enzymes, the altered expression of pro-apoptosis and tumor suppressor genes, or the increased activity of DNA repair mechanisms are frequently involved [3,4]. Recent evidence indicates that microRNAs (miRNAs) regulate these processes [5,6].…”

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confidence: 99%

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Yagüe

2015

Breast Cancer Res Treat

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Multidrug resistance (MDR) remains one of the most significant obstacles in breast cancer treatment, and this process often involves dysregulation of a great number of microRNAs (miRNAs). Some miRNAs are indicators of drug resistance and confer resistance to chemotherapeutic drugs, although our understanding of this complex process is still incomplete. We have used a combination of miRNA profiling and real-time PCR in two drug-resistant derivatives of MCF-7 and Cal51 cells. Experimental modulation of miR expression has been obtained by retroviral transfection. Taxol and doxorubicin IC50 values were obtained by short-term drug sensitivity assays. Apoptosis was determined by flow cytometry after annexin V staining, by caspase 3/7 and caspase 9 activity assays and the levels of apoptosis-related proteins bcl-2 and bax by real-time PCR and Western blot. miR target was studied using transient transfection of luciferase constructs with the 3 untranslated regions (UTR) of target mRNAs. Small interfering RNA-mediated genetic knock-down was performed in MDR cells and its modulatory effect on apoptosis examined. The effect of miRNA on tumorigenicity and tumor drug response was studied in mouse xenografts. miRNA profiling of two drug-resistant breast cancer cell models indicated that miR-218 was down-regulated in both MCF-7/A02 and CALDOX cells. Ectopic expression of miR-218 resensitized both drug-resistant cell lines to doxorubicin and taxol due to an increase in apoptosis. miR-218 binds survivin (BIRC5) mRNA 3-UTR and down-regulated reporter luciferase activity. Experimental down-regulation of survivin by RNA interference in drug-resistant cells did mimic the sensitization observed when miRNA-218 was up-regulated. In addition, resensitization to taxol was also observed in mouse tumor xenografts from cells over-expressing miR-218. miR-218 is involved in the development of MDR in breast cancer cells via targeting survivin and leading to evasion of apoptosis. Targeting miR-218 and survivin may thus provide a potential strategy for reversing drug resistance in breast cancer

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“…A number of studies have identified that histone methylation and miRNAs are essential in the initiation and progression of cancer (7)(8)(9). However, the association between SMYD3 and miRNAs is yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…miRNAs suppress gene expression by binding the targeted mRNA transcripts, which causes translational repression or mRNA degradation. Previous studies demonstrated that miRNAs serve important roles in tumorigenesis through the regulation of genes involved in cancer development and maintenance (7,8).A number of studies have identified that histone methylation and miRNAs are essential in the initiation and progression of cancer (7-9). However, the association between SMYD3 and miRNAs is yet to be elucidated.…”

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confidence: 99%

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Effect of SMYD3 on the microRNA expression profile of MCF-7 breast cancer cells

et al. 2017

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Abstract. SET and MYND domain containing 3 (SMYD3) is a histone methyltransferase (HMT) and transcription factor, which serves important roles in carcinogenesis. Numerous downstream target genes of SMYD3 have been identified in previous studies. However, the downstream microRNA (miRNA) s regulated by SMYD3 are yet to be elucidated. In the present study, the results of miRNA microarray demonstrated that 30 miRNA expression profiles were upregulated, whilst 24 miRNAs were downregulated by >2.0-fold in the SMYD3-overexpressed MCF-7 breast cancer cells. The HMT activity was demonstrated to be essential for SMYD3-mediated transactivation of miR-200c-3p and the overexpression of miR-200c-3p inhibited the transactivation effects of SMYD3 on myocardin-related transcription factor-A-dependent migration-associated genes. To our best knowledge, the current study is the first to report on the transcriptional regulation of SMYD3 on miRNAs, and miR-200c may be a downstream negative regulator of the SMYD3-mediated pathway in the migration of breast cancer cells. These results may provide a novel theoretical basis to understand the mechanisms underlying the initiation, progression, diagnosis, prevention and therapy of breast cancer. IntroductionSET and MYND domain containing 3 (SMYD3) is a novel histone methyltransferase gene identified in hepatoma and colon carcinoma cells by Hamamoto et al (1). SMYD3 is located on human chromosome 1 and encodes two protein isoforms that are composed of 428 and 369 amino acids. Previous studies have demonstrated that SMYD3 is frequently overexpressed in numerous types of cancer cells, including hepatic, colon, gastric and cervical carcinoma, and breast cancer (2-4), whilst the expression levels were lower in the corresponding normal tissue. A number of previous studies have demonstrated that SMYD3 has vital roles in the process of tumor development via its functions as a histone methylation enzyme and a transcription factor (5,6). SMYD3 modifies chromatin structure by catalyzing the methylation of histone H3 at lysine 4 (H3K4), H4K20 and H4K5 (5,6). Also, SMYD3 regulates the transcription of target genes via associating with RNA polymerase II or HELZ RNA helicase and binding at the motif CCCTCC or GGAGGG in the promoter (1).MicroRNAs (miRNAs) are small, non-coding, endogenous RNA molecules of 18-22 nucleotides that were first identified in Caenorhabditis elegans. miRNAs suppress gene expression by binding the targeted mRNA transcripts, which causes translational repression or mRNA degradation. Previous studies demonstrated that miRNAs serve important roles in tumorigenesis through the regulation of genes involved in cancer development and maintenance (7,8).A number of studies have identified that histone methylation and miRNAs are essential in the initiation and progression of cancer (7-9). However, the association between SMYD3 and miRNAs is yet to be elucidated. To investigate this further, the current study analyzed the global regulatory effects of SMYD3 on miRNAs in breast cancer cells usi...

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A summary for molecular regulations of miRNAs in breast cancer

Cited by 39 publications

References 147 publications

Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population

Associations of miRNA polymorphisms and expression levels with breast cancer risk in the Chinese population

miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer

Effect of SMYD3 on the microRNA expression profile of MCF-7 breast cancer cells

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