MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growth

Zhou, Boru; Ma, Ru; Si, Wenxia; Li, Sisi; Xu, Yan; Tu, Xin; Wang, Qing Kenneth

doi:10.1016/j.canlet.2013.01.028

Cited by 174 publications

(157 citation statements)

References 44 publications

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“…H9C2 cells were cultured in DMEM supplemented with 15% fetal bovine serum and transfected with siRNA using Lipofectamine 2000 according to the manufacturer's instructions (Invitrogen). After 48 h of transfection, cells were harvested for assaying siRNA knockdown efficiency using quantitative real-time RT-PCR and Western blotting analysis as described (4,(22)(23)(24)(25). Sequences of primers used for quantitative real-time PCR analysis are listed in Table 1.…”

Section: Methodsmentioning

confidence: 99%

αB-Crystallin Interacts with Nav1.5 and Regulates Ubiquitination and Internalization of Cell Surface Nav1.5

Huang

Wang

Liu

et al. 2016

Journal of Biological Chemistry

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Na v 1.5, the pore-forming ␣ subunit of the cardiac voltagegated Na ؉ channel complex, is required for the initiation and propagation of the cardiac action potential. Mutations in Na v 1.5 cause cardiac arrhythmias and sudden death. The cardiac Na ؉ channel functions as a protein complex; however, its complete components remain to be fully elucidated. A yeast two-hybrid screen identified a new candidate Na v 1.5-interacting protein, ␣B-crystallin. GST pull-down, co-immunoprecipitation, and immunostaining analyses validated the interaction between Na v 1.5 and ␣B-crystallin. Whole-cell patch clamping showed that overexpression of ␣B-crystallin significantly increased peak sodium current (I Na ) density, and the underlying molecular mechanism is the increased cell surface expression level of Na v 1.5 via reduced internalization of cell surface Na v 1.5 and ubiquitination of Na v 1.5. Knock-out of ␣B-crystallin expression significantly decreased the cell surface expression level of Na v 1.5. Co-immunoprecipitation analysis showed that ␣B-crystallin interacted with Nedd4-2; however, a catalytically inactive Nedd4-2-C801S mutant impaired the interaction and abolished the up-regulation of I Na by ␣B-crystallin. Na v 1.5 mutation V1980A at the interaction site for Nedd4-2 eliminated the effect of ␣B-crystallin on reduction of Na v 1.5 ubiquitination and increases of I Na density. Two disease-causing mutations in ␣B-crystallin, R109H and R151X (nonsense mutation), eliminated the effect of ␣B-crystallin on I Na . This study identifies ␣B-crystallin as a new binding partner for Na v 1.5. ␣B-Crystallin interacts with Na v 1.5 and increases I Na by modulating the expression level and internalization of cell surface Na v 1.5 and ubiquitination of Na v 1.5, which requires the protein-protein interactions between ␣B-crystallin and Na v 1.5 and between ␣B-crystallin and functionally active Nedd4-2.Na v 1.5 is the pore-forming ␣ subunit of the major cardiac voltage-gated Na ϩ channel complex. It generates the sodium current (I Na ) 4 that plays an essential role in the initiation and propagation of the cardiac action potential (1-3). Mutations in the SCN5A gene (encoding Na v 1.5) cause several inherited arrhythmias, including atrial fibrillation, Brugada syndrome, long QT syndrome, progressive cardiac conduction defect disease, sick sinus syndrome, and dilated cardiomyopathy (4). Na v 1.5 exists in vivo in a multiprotein complex, which interacts with the actin cytoskeleton and the extracellular matrix to provide an important functional link between channel complexes, cardiac structure, and electrical functioning (5, 6). Several proteins have been reported to bind to Na v 1.5 (5-7). We have previously reported a small protein, MOG1, with a function in nucleocytoplasmic protein transport that interacts directly with Na v 1.5, promotes trafficking of Na v 1.5 to the cell surface, and increases peak I Na density (4, 6). Specifically, MOG1 facilitates export of Na v 1.5 from the endoplasmic reticulum as well as targeting of Na v 1.5...

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Section: Methodsmentioning

confidence: 99%

αB-Crystallin Interacts with Nav1.5 and Regulates Ubiquitination and Internalization of Cell Surface Nav1.5

Huang

Wang

Liu

et al. 2016

Journal of Biological Chemistry

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“…23,24 Recently, several microRNAs, such as miR-195 and miR-503, were reported to regulate angiogenesis in tumor development. 17,19 In our previous study with the corneal suture model, we demonstrated that VEGF was significantly up-regulated. 15 In our present investigation with the transfection of mimic and inhibitor of miR-184, we showed that miR-184 negatively regulated VEGF expression levels and suppressed VEGF-induced endothelial cell tube formation.…”

Section: Discussionmentioning

confidence: 99%

“…[17][18][19] Here, we revealed by real-time PCR assay that the expression of frizzled-4 (Frz4), a member of frizzled receptor of the Wnt signaling pathway, was also upregulated in the corneal epithelia of rats after corneal suture surgery, compared with that in control rats (Fig. 1B).…”

Section: Corneal Suture Induces Mir-184 Down-regulation and Frizzled-mentioning

confidence: 99%

Down-Regulation of MicroRNA-184 Is Associated With Corneal Neovascularization

Zong

Zhou

Zhong

et al. 2016

Invest. Ophthalmol. Vis. Sci.

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“…miR-503 is downregulated in several types of cancer including oral, hepatocellular, gastric and endometrial [12,13,14,15,16] cancer, suggesting that it plays a tumor-suppressive role in carcinogenesis. In contrast, it is overexpressed in parathyroid carcinoma, retinoblastoma and adrenocortical carcinoma [17,18,19], and upregulation of miR-503 is associated with a shorter overall survival (OS) rate among patients with adrenocortical carcinoma [19].…”

Section: Introductionmentioning

confidence: 99%

miRNA-503 Promotes Tumor Progression and Is Associated with Early Recurrence and Poor Prognosis in Human Colorectal Cancer

et al. 2016

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Objectives: MicroRNA (miR)-503 is downregulated in several cancers and plays a tumor-suppressive role in carcinogenesis. However, the miR-503 expression pattern, its clinical significance and its molecular mechanism in colorectal cancer (CRC) have not been investigated. Methods: We analyzed miR-503 expression in normal mucosa (n = 20), adenoma (n = 27) and CRC (n = 20). We quantified miR-503 expression in an independent cohort (n = 191) and investigated the clinical significance of miR-503 in CRC. CRC cell lines were transfected with anti-miR-503 to assess its function and target gene. Results: miR-503 expression increased according to the adenoma-carcinoma sequence. High miR-503 expression was significantly associated with large tumor size, serosal invasion, lymphatic and venous invasion as well as lymph node metastasis. CRC patients with high miR-503 expression had significantly earlier relapse and poorer prognosis than those with low expression. miR-503 was an independent recurrence marker in stage I/II CRC. In vitro, attenuated miR-503 expression resulted in inhibition of proliferation, invasion and migration and acquisition of anoikis of CRC cells. The putative target gene (calcium-sensing receptor) was significantly upregulated after miR-503 attenuation. Conclusions: miR-503 acts as an ‘onco-miR' in CRC. High miR-503 expression is associated with early recurrence and poor prognosis in CRC.

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MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growth

Cited by 174 publications

References 44 publications

αB-Crystallin Interacts with Nav1.5 and Regulates Ubiquitination and Internalization of Cell Surface Nav1.5

αB-Crystallin Interacts with Nav1.5 and Regulates Ubiquitination and Internalization of Cell Surface Nav1.5

Down-Regulation of MicroRNA-184 Is Associated With Corneal Neovascularization

miRNA-503 Promotes Tumor Progression and Is Associated with Early Recurrence and Poor Prognosis in Human Colorectal Cancer

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