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      Meta-analysis of the association between three microRNA polymorphisms and breast cancer susceptibility

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          Single nucleotide polymorphisms (SNPs) in three microRNAs (miRNAs), rs2910164 in miR-146a, rs11614913 in miR-196a2, and rs3746444 in miR-499, have been associated with breast cancer (BC) susceptibility, but the evidence is conflicting. To obtain a more robust assessment of the association between these miRNA variants and BC risk, we carried out a meta-analysis through systematic literature retrieval from the PubMed and Embase databases. A total of 9 case-control studies on rs2910164, 12 on rs11614913, and 7 on rs3746444 were included. Pooled odds ratios and 95% confidence intervals were used to evaluate associations with BC risk. Overall analysis showed that rs2910164 was not associated with BC susceptibility in any genetic model, whereas rs11614913 was associated with a decreased risk in both the allelic contrast and recessive models, and rs3746444 imparted an increased risk in all genetic models. Stratified analyses showed that rs11614913 may decrease the risk of BC in the heterozygote model in Asians, and in all genetic models, except the heterozygote model, when the sample size is ≥ 500. Subgroup analysis indicated that rs3746444 was associated with increased risk of BC in Asians, but not Caucasians, at all sample sizes. This meta-analysis suggests that rs11614913 in miR-196a2 may decrease the risk of BC, while rs3746444 in miR-499 may increase it, especially in Asians when the sample size is large. We propose that rs11614913(C > T) and rs3746444 (A > G) may be useful biomarkers predictive of BC risk.

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          Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans.

          During C. elegans development, the temporal pattern of many cell lineages is specified by graded activity of the heterochronic gene Lin-14. Here we demonstrate that a temporal gradient in Lin-14 protein is generated posttranscriptionally by multiple elements in the lin-14 3'UTR that are regulated by the heterochronic gene Lin-4. The lin-14 3'UTR is both necessary and sufficient to confer lin-4-mediated posttranscriptional temporal regulation. The function of the lin-14 3'UTR is conserved between C. elegans and C. briggsae. Among the conserved sequences are seven elements that are each complementary to the lin-4 RNAs. A reporter gene bearing three of these elements shows partial temporal gradient activity. These data suggest a molecular mechanism for Lin-14p temporal gradient formation: the lin-4 RNAs base pair to sites in the lin-14 3'UTR to form multiple RNA duplexes that down-regulate lin-14 translation.
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            MicroRNA profiling: approaches and considerations.

            MicroRNAs (miRNAs) are small RNAs that post-transcriptionally regulate the expression of thousands of genes in a broad range of organisms in both normal physiological contexts and in disease contexts. miRNA expression profiling is gaining popularity because miRNAs, as key regulators in gene expression networks, can influence many biological processes and also show promise as biomarkers for disease. Technological advances have spawned a multitude of platforms for miRNA profiling, and an understanding of the strengths and pitfalls of different approaches can aid in their effective use. Here, we review the major considerations for carrying out and interpreting results of miRNA-profiling studies.
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              Genetic variation in microRNA networks: the implications for cancer research.

              Many studies have highlighted the role that microRNAs have in physiological processes and how their deregulation can lead to cancer. More recently, it has been proposed that the presence of single nucleotide polymorphisms in microRNA genes, their processing machinery and target binding sites affects cancer risk, treatment efficacy and patient prognosis. In reviewing this new field of cancer biology, we describe the methodological approaches of these studies and make recommendations for which strategies will be most informative in the future.

                Author and article information

                Impact Journals LLC
                15 September 2017
                16 June 2017
                : 8
                : 40
                : 68809-68824
                1 The Second Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
                2 Department of Breast Surgery, The First Hospital of Qinhuangdao, Qinhuangdao 066000, P.R. China
                3 Cancer Molecular Diagnostic Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, P.R. China
                4 Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
                Author notes
                Correspondence to: Jun-Tian Liu, ljt641024@
                Copyright: © 2017 Mu et al.

                This article is distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.


                Oncology & Radiotherapy

                breast cancer, meta-analysis, mirna, polymorphisms


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