Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK)

Luo, Jixian; Wang, Xiaoxiao; Xia, Zhibo; Yang, Lixuan; Ding, Zhi‐Ming; Chen, Shiyuan; Lai, Bingquan; Zhang, Nu

doi:10.1091/mbc.e14-10-1443

Cited by 53 publications

(37 citation statements)

References 52 publications

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“…Nucleolin has been previously described as an ITAF for virus IRESs such as poliovirus (20). Recently, it has been found to enhance cellular IRES-dependent translation of specificity protein-1 (Sp1), a transcription factor involved in tumor cells proliferation (22,39). These results are in accordance with findings showing that IRES-dependent translation initiation is regulated by ITAF's subcellular location (19).…”

Section: Discussionsupporting

confidence: 78%

Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

et al. 2016

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The vascular endothelial growth factor VEGF-D promotes metastasis by inducing lymphangiogenesis and dilatation of the lymphatic vasculature, facilitating tumor cell extravasion. Here we report a novel level of control for VEGF-D expression at the level of protein translation. In human tumor cells, VEGF-D colocalized with eIF4GI and 4E-BP1, which can program increased initiation at IRES motifs on mRNA by the translational initiation complex. In murine tumors, the steady-state level of VEGF-D protein was increased despite the overexpression and dephosphorylation of 4E-BP1, which downregulates protein synthesis, suggesting the presence of an internal ribosome entry site (IRES) in the 5 0 UTR of VEGF-D mRNA. We found that nucleolin, a nucleolar protein involved in ribosomal maturation, bound directly to the 5 0 UTR of VEGF-D mRNA, thereby improving its translation following heat shock stress via IRES activation. Nucleolin blockade by RNAi-mediated silencing or pharmacologic inhibition reduced VEGF-D translation along with a subsequent constriction of lymphatic vessels in tumors. Our results identify nucleolin as a key regulator of VEGF-D expression, deepening understanding of lymphangiogenesis control during tumor formation.

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Section: Discussionsupporting

confidence: 78%

Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

et al. 2016

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“…The [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] MTS viability assay (Promega) was performed according to standard methods as described previously (Luo et al, 2015). ZKSCAN1 and circZKSCAN1 knockdown or overexpression cell lines and control cells were seeded at 2 9 10 4 cells in 100 lL medium per well of a 96well plate Corning Incorporated (Corning, NY, USA) for the MTS assay (Qi et al, 2014;Qin et al, 2016).…”

Section: Cell Proliferation Migration and Invasion Assaymentioning

confidence: 99%

ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways

et al. 2017

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There is increasing evidence that circular RNA (circRNA) are involved in cancer development, but the regulation and function of human circRNA remain largely unknown. In this study, we demonstrated that ZKSCAN1, a zinc finger family gene, is expressed in both linear and circular (circZKSCAN1) forms of RNA in human hepatocellular carcinoma (HCC) tissues and cell lines. Here, we analyzed a cohort of 102 patients and found that expression of both ZKSCAN1 mRNA and circZKSCAN1 was significantly lower (P < 0.05) in the HCC samples compared with that in matched adjacent nontumorous tissues by reverse transcription PCR (RT‐PCR). The low expression level of ZKSCAN1 was only associated with tumor size (P = 0.032), while the cirZKSCAN1 levels varied in patients with different tumor numbers (P < 0.01), cirrhosis (P = 0.031), vascular invasion (P = 0.002), or microscopic vascular invasion (P = 0.002), as well as with the tumor grade (P < 0.001). Silencing both ZKSCAN1 mRNA and circZKSCAN1 promoted cell proliferation, migration, and invasion. In contrast, overexpression of both forms of RNA repressed HCC progression in vivo and in vitro. Silencing or overexpression of both forms of RNA did not interfere with each other. RNA‐seq revealed a very different molecular basis for the observed effects; ZKSCAN1 mRNA mainly regulated cellular metabolism, while circZKSCAN1 mediated several cancer‐related signaling pathways, suggesting a nonredundant role for ZKSCAN1 mRNA and circRNA. In conclusion, our results revealed two post‐translational products (ZKSCAN1 mRNA and circZKSCAN1) that cooperated closely with one another to inhibit growth, migration, and invasion of HCC. cirZKSCAN1 might be a useful marker for the diagnosis of HCC.

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“…In all networks, the most connected TF targeted by the studied miRNAs was Sp1 with 12, 32, and 32 connections in the PPI, hESCT0, and fBrain networks, respectively—Figure and Supporting Information Figure S5. Sp1 has been described as a promoter of proliferation and stem cell marker in glioma cells but it is still poorly characterized in neurogenesis.…”

Section: Resultsmentioning

confidence: 99%

miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network

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et al. 2015

Stem Cells

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The ventricular-subventricular zone harbors neural stem cells (NSCs) that can differentiate into neurons, astrocytes, and oligodendrocytes. This process requires loss of stem cell properties and gain of characteristics associated with differentiated cells. miRNAs function as important drivers of this transition; miR-124, -128, and -137 are among the most relevant ones and have been shown to share commonalities and act as proneurogenic regulators. We conducted biological and genomic analyses to dissect their target repertoire during neurogenesis and tested the hypothesis that they act cooperatively to promote differentiation. To map their target genes, we transfected NSCs with antagomiRs and analyzed differences in their mRNA profile throughout differentiation with respect to controls. This strategy led to the identification of 910 targets for miR-124, 216 for miR-128, and 652 for miR-137. The target sets show extensive overlap. Inspection by gene ontology and network analysis indicated that transcription factors are a major component of these miRNAs target sets. Moreover, several of these transcription factors form a highly interconnected network. Sp1 was determined to be the main node of this network and was further investigated. Our data suggest that miR-124, -128, and -137 act synergistically to regulate Sp1 expression. Sp1 levels are dramatically reduced as cells differentiate and silencing of its expression reduced neuronal production and affected NSC viability and proliferation. In summary, our results show that miRNAs can act cooperatively and synergistically to regulate complex biological processes like neurogenesis and that transcription factors are heavily targeted to branch out their regulatory effect. STEM CELLS 2016;34:220-232 SIGNIFICANCE STATEMENTWe demonstrate here, perhaps for the first time, that miRNAs (miR-124, -128 and -137) can act cooperatively to regulate a complex biological problem such as neurogenesis. They do so by targeting overlapping sets of genes. Moreover, our genomic analyses determined that transcription factors are the main component of their target sets. Our results indicate additional associations between the three analyzed miRNA and the targeted TFs. Based on described ChIP analysis, we suggest that miR-124, -128 and -137 and their targeted TFs could act on overlapping and related target sets producing different functional outcomes that ultimately would influence the balance self-renewal/differentiation.

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Transcriptional factor specificity protein 1 (SP1) promotes the proliferation of glioma cells by up-regulating midkine (MDK)

Abstract: Midkine (MDK) expression is associated with the proliferation of many cancers, including glioma. SP1 directly up-regulates the expression of MDK, and the SP1-MDK axis cooperates in glioma tumorigenesis.

Cited by 53 publications

References 52 publications

Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

Nucleolin Promotes Heat Shock–Associated Translation of VEGF-D to Promote Tumor Lymphangiogenesis

ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways

miR-124, -128, and -137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network

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