The transcription factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth factor-A to inhibit neovascularization in vivo

Merdzhanova, Galina; Gout, Stéphanie; Kéramidas, Michelle; Edmond, Valérie; Coll, Jean‐Luc; Brambilla, Christian; Brambilla, Élisabeth; Gazzéri, Sylvie; Eymin, Béatrice

doi:10.1038/onc.2010.281

Cited by 71 publications

(66 citation statements)

References 29 publications

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“…Mutations of Wilms' tumor suppressor gene (WT1) lead to the up-regulation of SRPK1, which diminishes the SRSF1-mediated up-regulation of VEGF165b (Amin et al 2011). The elevated ratio of VEGF165 to VEGF165b correlates closely with the angiogenesis which facilitates the tumor growth (Merdzhanova et al 2010). Elevated SRPK1 modulates the influence of SRSF2 on caspase-8 mRNA splicing and subsequently strengthens the therapeutic resistance of cancer cells to cisplatin treatment (Edmond et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events

Lin

Tarn

et al. 2014

RNA

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Imbalanced splicing of premessenger RNA is typical of tumorous malignancies, and the regulatory mechanisms involved in several tumorigenesis-associated splicing events are identified. Elevated expression of serine-arginine protein kinase 1 (SRPK1) may participate in the pathway responsible for the dysregulation of splicing events in malignant tumor cells. In this study, we observed a correlation between the cytoplasmic accumulation of RNA-binding motif protein 4 (RBM4) and up-regulated SRPK1 in breast cancer cells. The production of the IR-B and MCL-1 S transcripts was induced separately by the overexpression of RBM4 and SRPK1 gene silencing. Overexpressed RBM4 simultaneously bound to the CU-rich elements within the MCL-1 exon2 and the downstream intron, which subsequently facilitated the exclusion of the regulated exon. Breast cancer cells are deprived of apoptotic resistance through the RBM4-mediated up-regulation of the IR-B and MCL-1 S transcripts. These findings suggest that the splicing events regulated by the SRPK1-RMB4 network may contribute to tumorigenesis through altered sensitivity to apoptotic signals in breast cancer cells.

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Section: Discussionmentioning

confidence: 99%

Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events

Lin

Tarn

et al. 2014

RNA

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“…In the present study, let7g treatment increased VEGF-A 164a levels but decreased VEGF-A 165b levels in murine ischaemic limb model. The ratio of VEGF-A 165b and VEGF-A 164a can be determined by SC35, which is a pre-mRNA splicing factor for alternative processing at VEGF-A exon 8 [19]. The SC35 protein was reported to increase the VEGF-A 165b /VEGF-A ratio and to decrease tumour neovascularization in immune-deficient nude mice [19].…”

Section: Discussionmentioning

confidence: 99%

“…The ratio of VEGF-A 165b and VEGF-A 164a can be determined by SC35, which is a pre-mRNA splicing factor for alternative processing at VEGF-A exon 8 [19]. The SC35 protein was reported to increase the VEGF-A 165b /VEGF-A ratio and to decrease tumour neovascularization in immune-deficient nude mice [19]. Our data demonstrated that let-7g down-regulated the CDK6/ SC35/VEGF-A 165b cascade and up-regulated the expression of total VEGF-A as well as the VEGF-A 164a isoform.…”

Section: Discussionmentioning

confidence: 99%

Section: Let-7g Enhances Vegf-a Alternative Splicing Through Modulatimentioning

confidence: 99%

“…the rodent ortholog of human VEGF-A 165a ) and VEGF-A 165b isoforms [19]. SC35 was found to be a transcription target of E2F1, and E2F1 increased the expression of SC35 in cellular models [19,20]. Using IPA, let-7g was predicted to directly suppress CDK6, which inhibited the release of E2F1 and subsequently down-regulated SC35 expression [21,22].…”

Section: Let-7g Enhances Vegf-a Alternative Splicing Through Modulatimentioning

confidence: 99%

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MicroRNA let‐7g possesses a therapeutic potential for peripheral artery disease

Hsu

Hsi

Wang

et al. 2016

J Cellular Molecular Medi

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Peripheral artery disease (PAD) is a manifestation of systemic atherosclerosis and conveys a significant health burden globally. Critical limb ischaemia encompasses the most severe consequence of PAD. Our previous studies indicate that microRNA let-7g prevents atherosclerosis and improves endothelial functions. This study aimed to investigate whether and how let-7g therapy may improve blood flow to ischaemic limbs. The present study shows that let-7g has multiple pro-angiogenic effects on mouse ischaemic limb model and could be a potential therapeutic agent for PAD. Mice receiving intramuscular injection of let-7g had more neovascularization, better local perfusion and increased recruitment of endothelial progenitor cells after hindlimb ischaemia. The therapeutic effects of let-

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Physiological Role of Vascular Endothelial Growth Factors as Homeostatic Regulators

Bates

Beazley‐Long

Benest

et al. 2018

Comprehensive Physiology

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The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through their actions on vascular cells, but also through direct actions on other tissue types, including epithelial cells, neurons, and the immune system. The complexity of the five members of the gene family in terms of their different splice isoforms, differential translation, and specific localizations have enabled tissues to use these potent signaling molecules to control how they function to maintain their environment. This homeostatic function of VEGFs has been less intensely studied than their involvement in disease processes, development, and reproduction, but they still play a substantial and significant role in healthy control of blood volume and pressure, interstitial volume and drainage, renal and lung function, immunity, and signal processing in the peripheral and central nervous system. The widespread expression of VEGFs in healthy adult tissues, and the disturbances seen when VEGF signaling is inhibited support this view of the proteins as endogenous regulators of normal physiological function. This review summarizes the evidence and recent breakthroughs in understanding of the physiology that is regulated by VEGF, with emphasis on the role they play in maintaining homeostasis. © 2017 American Physiological Society. Compr Physiol 8:955-979, 2018.

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The transcription factor E2F1 and the SR protein SC35 control the ratio of pro-angiogenic versus antiangiogenic isoforms of vascular endothelial growth factor-A to inhibit neovascularization in vivo

Cited by 71 publications

References 29 publications

Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events

Elevated SRPK1 lessens apoptosis in breast cancer cells through RBM4-regulated splicing events

MicroRNA let‐7g possesses a therapeutic potential for peripheral artery disease

Physiological Role of Vascular Endothelial Growth Factors as Homeostatic Regulators

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