Soluble syntaxin 3 functions as a transcriptional regulator

Giovannone, Adrian J.; Winterstein, Christine; Bhattaram, Pallavi; Reales, Elena; Low, Seng Hui; Baggs, Julie E.; Xu, Mimi; Lalli, Matthew A.; Hogenesch, John B.; Weimbs, Thomas

doi:10.1074/jbc.ra117.000874

Cited by 15 publications

(10 citation statements)

References 54 publications

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“…STX3 also functions as a transcriptional regulator. Breast cancer patients with STX3 overexpression had advanced TNM stage and shorter overall and disease-free survival compared with patients with low STX3 expression 30. STX3 also promoted the proliferation of breast cancer cells by increasing activation of Akt-mTOR signaling 31.…”

Section: Discussionmentioning

confidence: 97%

<p>Upregulation of long noncoding RNA LINC00152 promotes proliferation and metastasis of esophageal squamous cell carcinoma</p>

Yang¹,

Sun²,

Chi³

et al. 2019

CMAR

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Purpose: Esophageal cancer is a major cause of cancer-related mortality worldwide. The long noncoding RNA LINC00152 has been confirmed to play an oncogenic role in many cancers. However, the expression pattern and function of LINC00152 in human esophageal squamous cell carcinoma (ESCC) remain unclear. Materials and methods: We evaluated LINC00152 expression in ESCC by qPCR and in situ hybridization. Proliferation, apoptosis, cell cycle, migration and invasion were examined in ESCC cells knocked down for LINC00152 knockdown by siRNA. Furthermore, an mRNA microarray was performed in ESCC cells with LINC00152 knockdown. Results: LINC00152 was significantly upregulated in human ESCC clinical samples ( P <0.001) and cell lines ( P =0.008), and LINC00152 overexpression was related to lymphatic metastasis ( P =0.03) and advanced pTNM classification ( P =0.005). Furthermore, ESCC patients with LINC00152 overexpression had significantly shorter overall survival ( P =0.007), and LINC00152 overexpression was an independent risk factor for overall survival of ESCC patients. LINC00152 knockdown inhibited the proliferation, migration and invasion of ESCC cells in vitro. In addition, mechanistic investigations through mRNA array and immunoblot analyses demonstrated that LINC00152 regulated the expression of several cell cycle-related proteins and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) interactions in vesicular transport pathway proteins. Conclusion: Our research indicated that LINC00152 exhibits oncogenic functions in ESCC and may represent a potential new target for ESCC therapy.

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Section: Discussionmentioning

confidence: 97%

<p>Upregulation of long noncoding RNA LINC00152 promotes proliferation and metastasis of esophageal squamous cell carcinoma</p>

Yang¹,

Sun²,

Chi³

et al. 2019

CMAR

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“…7; Table 4). A SNARE protein gene on the list, stx3a, was recently shown to produce a protein isoform in humans that, in epithelial tissue culture, could regulate gene expression through interactions with the transcription factor ETV4 (Giovannone et al, 2018).…”

Section: Identification Of Possible Novel Regulators Of Lens Developmentmentioning

confidence: 99%

Single cell transcriptomics of the developing zebrafish lens and identification of putative controllers of lens development

Farnsworth

Posner

Miller

2021

Experimental Eye Research

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The vertebrate lens is a valuable model system for investigating the gene expression changes that coordinate tissue differentiation due to its inclusion of two spatially separated cell types, the outer epithelial cells and the deeper denucleated fiber cells that they support. Zebrafish are a useful model system for studying lens development given the organ's rapid development in the first several days of life in an accessible, transparent embryo. While we have strong foundational knowledge of the diverse lens crystallin proteins and the basic gene regulatory networks controlling lens development, no study has detailed gene expression in a vertebrate lens at single cell resolution. Here we report an atlas of lens gene expression in zebrafish embryos at single cell resolution through five days of development, identifying a number of novel regulators of lens development as potential targets for future functional studies. Our temporospatial expression data address open questions about the function of α-crystallins during lens development and provides the first detailed view of β-and γ-crystallin expression in and outside the lens. We describe subfunctionalization in transcription factor genes that occur as paralog pairs in the zebrafish. Finally, we examine the expression dynamics of cytoskeletal, RNA-binding, and transcription factors genes, identifying a number of novel patterns. Overall these data provide a foundation for identifying and characterizing lens developmental regulatory mechanisms and revealing targets for future functional studies with potential therapeutic impact.

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“…We next compared the relative levels of STX3A and STX3B mRNA in the human retina by analyzing the presence of splice junctions specific for the two isoforms in RNA-seq data sets from six normal human retina samples (Ratnapriya et al 2019 ), and included a soluble form of STX3 , STX3S that is generated by splicing together exons 9A and 11A and skipping exon 10A (Giovannone et al 2018 ). These data demonstrate that STX3B is the major human retinal transcript (Fig.…”

Section: Resultsmentioning

confidence: 99%

Pathogenic STX3 variants affecting the retinal and intestinal transcripts cause an early-onset severe retinal dystrophy in microvillus inclusion disease subjects

et al. 2021

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Biallelic STX3 variants were previously reported in five individuals with the severe congenital enteropathy, microvillus inclusion disease (MVID). Here, we provide a significant extension of the phenotypic spectrum caused by STX3 variants. We report ten individuals of diverse geographic origin with biallelic STX3 loss-of-function variants, identified through exome sequencing, single-nucleotide polymorphism array-based homozygosity mapping, and international collaboration. The evaluated individuals all presented with MVID. Eight individuals also displayed early-onset severe retinal dystrophy, i.e., syndromic—intestinal and retinal—disease. These individuals harbored STX3 variants that affected both the retinal and intestinal STX3 transcripts, whereas STX3 variants affected only the intestinal transcript in individuals with solitary MVID. That STX3 is essential for retinal photoreceptor survival was confirmed by the creation of a rod photoreceptor-specific STX3 knockout mouse model which revealed a time-dependent reduction in the number of rod photoreceptors, thinning of the outer nuclear layer, and the eventual loss of both rod and cone photoreceptors. Together, our results provide a link between STX3 loss-of-function variants and a human retinal dystrophy. Depending on the genomic site of a human loss-of-function STX3 variant, it can cause MVID, the novel intestinal-retinal syndrome reported here or, hypothetically, an isolated retinal dystrophy.

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Soluble syntaxin 3 functions as a transcriptional regulator

Cited by 15 publications

References 54 publications

<p>Upregulation of long noncoding RNA LINC00152 promotes proliferation and metastasis of esophageal squamous cell carcinoma</p>

<p>Upregulation of long noncoding RNA LINC00152 promotes proliferation and metastasis of esophageal squamous cell carcinoma</p>

Single cell transcriptomics of the developing zebrafish lens and identification of putative controllers of lens development

Pathogenic STX3 variants affecting the retinal and intestinal transcripts cause an early-onset severe retinal dystrophy in microvillus inclusion disease subjects

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