Current Evidence and Future Perspectives on HuR and Breast Cancer Development, Prognosis, and Treatment

Kotta‐Loizou, Ioly; Vasilopoulos, Spyridon N.; Coutts, Robert H.A.; Theocharis, Stamatios

doi:10.1016/j.neo.2016.09.002

Cited by 47 publications

(47 citation statements)

References 122 publications

(211 reference statements)

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“…HuR binds to mRNA and has been shown to regulate various genes implicated in cancer formation, progression, metastasis, and prognosis . Our previous study has shown that anti‐inflammatory cytokine (IL‐10) administration in mice decreases myocardial HuR expression and attenuates cardiac remodeling and dysfunction .…”

Section: Resultsmentioning

confidence: 99%

“…Among the RBPs, human antigen R (HuR; encoded by the ELAVL1 gene) is ubiquitously expressed and binds to AU‐Rich Elements (ARE) in the 3′‐untranslated region (3′UTR) of mRNA and confers its stability . HuR regulation of cancer progression and pathology has been extensively studied . While the regulatory role of HuR in cardiovascular pathophysiology is slowly emerging, we and other research groups have demonstrated the involvement of HuR in hyperglycemia‐mediated human ventricular cardiomyocyte pyroptosis, rat myocyte hypertrophic growth, inflammation, and cell proliferation/death .…”

Section: Introductionmentioning

confidence: 99%

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Targeting exosome‐associated human antigen R attenuates fibrosis and inflammation in diabetic heart

et al. 2019

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RNA‐binding proteins like human antigen R (HuR) are key regulators in post‐transcriptional control of gene expression in several pathophysiological conditions. Diabetes adversely affects monocyte/macrophage biology and function. It is not known whether diabetic milieu affects cellular/exosome‐HuR and its implications on cardiac inflammation and fibrosis. Here, we evaluate in vitro and in vivo effects of diabetic milieu on macrophage cellular/exosome‐HuR, alterations in intercellular cross talk with fibroblasts, and its impact on cardiac remodeling. Human failing hearts show higher HuR levels. Diabetic milieu activates HuR expression in cardiac‐ and cultured bone marrow‐derived macrophages (BMMØ) and stimulates HuR nuclear‐to‐cytoplasmic translocation and exosome transfer. Exosomes from macrophages exposed to diabetic milieu (high glucose or db/db mice) significantly increase inflammatory and profibrogenic responses in fibroblast (in vitro) and cardiac fibrosis in mice. Intriguingly, Exo‐HuR deficiency (HuR knockdown in macrophage) abrogates the above effects. In diabetic mice, macrophage depletion followed by reconstitution with BMMØ‐derived HuR‐deficient exosomes inhibits angiotensin II‐induced cardiac fibrosis response and preserves left ventricle function as compared to control‐exosome administration. To the best of our knowledge, this is the first study to demonstrate that diabetes activates BMMØ HuR expression and its transfer into exosome. The data suggest that HuR might be targeted to alleviate macrophage dysfunction and pathological fibrosis in diabetes.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting exosome‐associated human antigen R attenuates fibrosis and inflammation in diabetic heart

et al. 2019

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“…Kim et al demonstrated that high levels of OIP5‐AS1 could increase HuR‐OIP5‐AS1 complexes and prevent HuR interaction with target mRNAs . Furthermore, HuR is highly rich in tumor tissues, and HuR target mRNAs can encode proteins that are associated with tumorigenesis, including cell proliferation and angiogenesis . Moreover, OIP5‐AS1 can suppress cell proliferation by reducing GAK levels …”

Section: Mechanisms Of Lncrnas In MMmentioning

confidence: 99%

“…68 Furthermore, HuR is highly rich in tumor tissues, and HuR target mRNAs can encode proteins that are associated with tumorigenesis, including cell proliferation and angiogenesis. 69 Moreover, OIP5-AS1 can suppress cell proliferation by reducing GAK levels. 70 In MM, downregulated OIP5-AS1 can increase the level of miR-410.…”

Section: Oip5-as1mentioning

confidence: 99%

The role of long non‐coding RNAs in multiple myeloma

Cui

Song

Fang

2019

European J of Haematology

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Multiple myeloma (MM) is still an incurable disease, and its pathogenesis involves cytogenetics and epigenetics. In recent years, the roles of long non‐coding RNAs (lncRNAs) in MM have been deeply studied by scholars. LncRNAs are defined as a class of non‐protein‐coding transcripts greater than 200 nucleotides in length, which are involved in a large spectrum of biological processes, including proliferation, differentiation, apoptosis, invasion, and chromatin remodeling. However, little is known about the specific mechanisms of these lncRNAs. They can act as oncogenic and/or tumor‐suppressive factors in the development and progression of MM. But that how do they work remains unclear. In this review, the recent progress in the study of functional lncRNAs associated with MM was summarized and the present knowledge about their expression and roles was discussed, to provide guidance for the in‐depth functional study of lncRNAs.

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“…Breast cancer (BC) is the most common malignancy among females worldwide, and is a heterogeneous and multiplex disease with multiple pathogenic factors [15][16][17]. The 5-year survival of BC will be greatly improved if the disease is diagnosed at an early stage, yet the outcome of 15% of BC patients is still poor due to diagnosis at an advanced stage [18][19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

The Clinicopathological Significance and Correlative Signaling Pathways of an Autophagy-Related Gene, Ambra1, in Breast Cancer: a Study of 25 Microarray RNA-Seq Datasets and in-House Gene Silencing

Xiong

et al. 2018

Cell Physiol Biochem

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Background/Aims: The activating molecule in Beclin1-regulated autophagy (Ambra1) has been observed to be over-expressed in several cancers, but the clinical contribution of Ambra1 in breast cancer (BC) remains unknown. Hence, in this study, we conducted a comprehensive investigation into the expression, biological role, and underlying functional mechanism of Ambra1 in BC. Methods: Microarray and RNA-seq datasets providing Ambra1 expression data were obtained from Gene Expression Omnibus (GEO), ArrayExpress, Oncomine, and The Cancer Genome Atlas (TCGA). Both standard mean deviation (SMD) and summary receiver operating characteristic methods were employed to assess Ambra1 expression in BC. We then silenced Ambra1 in MDA-MB-231 cells and performed in vitro experiments to explore the biological effects of Ambra1 on BC cells. Furthermore, differentially expressed genes (DEGs) after Ambra1 knock-down were profiled with a microarray and overlapped with the genes correlated with Ambra1 from Multi Experiment Matrix (MEM) and genes similar to Ambra1 from Gene Expression Profiling Interactive Analysis. These overlapping genes were collected for further bioinformatics analyses to investigate the underlying molecular mechanism of Ambra1 in BC. Results: A total of 25 microarray and RNA-seq datasets involving 2460 breast cancer samples were included. The pooled results demonstrated that Ambra1 was markedly up-regulated in BC tissues (SMD=0.39, 95% CI=0.15–0.63; P=0.002), and the Ambra1 level was also significantly related to the progression of BC, especially metastasis status (P=0.004). In vitro experiments suggested that the proliferation of MDA-MB-231 cells transfected with Ambra1 short hairpin RNA (sh-RNA 2450) showed a decreasing trend at 48 h compared with the control (CK) group. However, apoptosis was similar in cells transfected with Ambra1 sh-RNAs and in the CK cells. Furthermore, we performed a microarray-based comparison of genes after Ambra1 knock-down. The 828 DEGs from microarray analysis were intersected with 4266 Ambra1 co-expressed genes from MEM. Eventually, the overlapped 183 genes were found to be enriched in several well-known cancer-related pathways, including the MAPK signaling pathway, chronic myeloid leukemia pathway, and VEGF signaling pathway. Conclusion: These results indicate that the level of Ambra1 up-regulation is clearly related to tumorigenesis and progression of BC, probably via influencing several vital pathways. However, this hypothesis needs to be validated with more in-depth experiments in the future.

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Current Evidence and Future Perspectives on HuR and Breast Cancer Development, Prognosis, and Treatment

Cited by 47 publications

References 122 publications

Targeting exosome‐associated human antigen R attenuates fibrosis and inflammation in diabetic heart

Targeting exosome‐associated human antigen R attenuates fibrosis and inflammation in diabetic heart

The role of long non‐coding RNAs in multiple myeloma

The Clinicopathological Significance and Correlative Signaling Pathways of an Autophagy-Related Gene, Ambra1, in Breast Cancer: a Study of 25 Microarray RNA-Seq Datasets and in-House Gene Silencing

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