Antagonistic Function of the RNA-binding Protein HuR and miR-200b in Post-transcriptional Regulation of Vascular Endothelial Growth Factor-A Expression and Angiogenesis

Chang, Sung-Hee; Lu, Yi-Chien; Li, Xi; Hsieh, Wan-Ying; Xiong, Ye; Ghosh, Monisha; Evans, Todd; Elemento, Olivier; Hla, Timothy

doi:10.1074/jbc.m112.423871

Cited by 77 publications

(68 citation statements)

References 53 publications

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“…VEGF is tightly regulated at the transcript level, and although its reported half-life is short (15-40 min in vitro),this can be substantially extended during periods of hypoxia and nutrient withdrawal (Ikeda et al 1995, Shima et al 1995, Levy et al 1996, Dibbens et al 1999). AU-rich elements within the 3 0 UTR of the VEGF transcript, along with other elements within the coding and UTRs, are potential targets for a range of RNA-binding proteins that have been shown to result in both positive and negative effects on transcript stability (Claffey et al 1998, Shih & Claffey 1999, King 2000, Goldberg-Cohen et al 2002, Coles et al 2004, Onesto et al 2004, Fellows et al 2012, Chang et al 2013. Hypoxia-dependent regulation of transcript stability has been well characterized in a number of cancer types and was recently reviewed by Arcondeguy et al (2013).…”

Section: Post-transcriptional Regulation Of Vegf Signaling In Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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Prostate cancer (PCa) is the most common malignancy affecting men in the western world. Although radical prostatectomy and radiation therapy can successfully treat PCa in the majority of patients, up to w30% will experience local recurrence or metastatic disease. Prostate carcinogenesis and progression is typically an androgen-dependent process. For this reason, therapies for recurrent PCa target androgen biosynthesis and androgen receptor function. Such androgen deprivation therapies (ADT) are effective initially, but the duration of response is typically %24 months. Although ADT and taxane-based chemotherapy have delivered survival benefits, metastatic PCa remains incurable. Therefore, it is essential to establish the cellular and molecular mechanisms that enable localized PCas to invade and disseminate. It has long been accepted that metastases require angiogenesis. In the present review, we examine the essential role for angiogenesis in PCa metastases, and we focus in particular on the current understanding of the regulation of vascular endothelial growth factor (VEGF) in localized and metastatic PCa. We highlight recent advances in understanding the role of VEGF in regulating the interaction of cancer cells with tumor-associated immune cells during the metastatic process of PCa. We summarize the established mechanisms of transcriptional and post-transcriptional regulation of VEGF in PCa cells and outline the molecular insights obtained from preclinical animal models of PCa. Finally, we summarize the current state of anti-angiogenesis therapies for PCa and consider how existing therapies impact VEGF signaling.

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Section: Post-transcriptional Regulation Of Vegf Signaling In Pcamentioning

confidence: 99%

Regulation of vascular endothelial growth factor in prostate cancer

Brot¹,

Ntekim²,

Cardenas³

et al. 2015

Endocrine-Related Cancer

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“…Recently, it was reported that iNOS expression was downregulated in bone marrow-derived macrophages from myeloidspecific HuR knockout mice (Elavl1Mø KO), indicating that HuR stabilizes iNOS mRNA in macrophages in vivo (Chang et al, 2013). Accordingly, we focused on HuR as a target of berberine for the destabilization of iNOS mRNA and by using an RNA interference strategy, sought to determine whether berberine could control iNOS mRNA stability via HuR regulation.…”

Section: Discussionmentioning

confidence: 99%

Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages

Shin

Choi

Seo

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Berberine, a major isoquinoline alkaloid found in medicinal herbs, has been reported to possess anti-inflammatory effects; however, the underlying mechanisms responsible for its actions are poorly understood. In the present study, we investigated the inhibitory effects of berberine and the molecular mechanisms involved in lipopolysaccharide (LPS)-treated RAW 264.7 and THP-1 macrophages and its effects in LPS-induced septic shock in mice. In both macrophage cell types, berberine inhibited the LPS-induced nitric oxide (NO) production and inducible NO synthase (iNOS) protein expression, but it had no effect on iNOS mRNA transcription. Suppression of LPS-induced iNOS protein expression by berberine occurred via a human antigen R (HuR)-mediated reduction of iNOS mRNA stability. Molecular data revealed that the suppression on the LPS-induced HuR binding to iNOS mRNA by berberine was accompanied by a reduction in nucleocytoplasmic HuR shuttling. Pretreatment with berberine reduced LPS-induced iNOS protein expression and the cytoplasmic translocation of HuR in liver tissues and increased the survival rate of mice with LPS-induced endotoxemia. These results show that the suppression of iNOS protein expression by berberine under LPS-induced inflammatory conditions is associated with a reduction in iNOS mRNA stability resulting from inhibition of the cytoplasmic translocation of HuR.

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“…In the meantime, other researchers also reported that miR-200c promotes mesodermal specification while repressing neuroectodermal differentiation from ESCs [95], suggesting that miR-200c may play a cell-autonomous role in mediating EC differentiation from stem cells. Interestingly, miR-200b displays an antiangiogenic activity in tumor and in embryonic vascular development [96,97], partially through repressing the crucial endothelial lineage related transcription factor E26 oncogene homolog 1 (Ets-1) [98]. This may reflect the distinct functions and dynamic regulation of miR-200 family members in EC differentiation, behaviors and embryonic vascular development at different stages.…”

Section: Mir-200 Familymentioning

confidence: 99%

MicroRNAs in Endothelial Development and Differentiation

Yang¹

2014

J Stem Cell Res Ther

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Endothelial integrity or homeostasis is not only essential for regulating arterial activity and vascular tone under physiological conditions, but also critical for triggering various cardiovascular diseases including atherosclerosis and balloon angioplasty if such a balance has been impaired. Moreover, endothelial cell development and differentiation are key steps during embryogenesis and involves co-ordinations of diverse signaling molecules and transcription factors. Therefore, characterizing the molecular mechanisms underlying endothelial differentiation and development will not only improve our understanding of pathogenesis of vascular disease, but also facilitate our ability in generation of vessels cells from pluripotent stem cells for therapeutic purpose. MicroRNAs, a class of small, non-coding RNAs, have been extensively implicated in the regulation of various aspects of biological processes such as embryonic development, tissue/organ homeostasis, and metabolism, as well as almost all the human disease, particularly cancers and cardiovascular diseases. Accumulating evidence has implicated that microRNAs play an important role in regulation of endothelial development, phenotype and function. In this review, we will summarize new findings from recent studies in this field and discuss our current understanding of how microRNAs regulate endothelial development and differentiation from stem cells.

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Antagonistic Function of the RNA-binding Protein HuR and miR-200b in Post-transcriptional Regulation of Vascular Endothelial Growth Factor-A Expression and Angiogenesis

Cited by 77 publications

References 53 publications

Regulation of vascular endothelial growth factor in prostate cancer

Regulation of vascular endothelial growth factor in prostate cancer

Berberine Decreased Inducible Nitric Oxide Synthase mRNA Stability through Negative Regulation of Human Antigen R in Lipopolysaccharide-Induced Macrophages

MicroRNAs in Endothelial Development and Differentiation

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