Biology subjects

Gong, D.

Publications and source records attributed to Gong, D..

4 recordsLinked to original sources

bioRxiv2018

Preclinical Study: Sunitinib-suppressed MiR-452-5p Facilitates Renal Cancer Cell Invasion and Metastasis Through Modulating SMAD4/SMAD7/EMT Signals

Although microRNAs (miRNAs) have been revealed as crucial modulators in tumor metastasis and target therapy, our understanding of their roles in metastatic renal cell carcinoma (mRCC) and Sunitinib treatment is limited. Here, We focused on 2 published microarray data to select out our anchored miRNA which was downregulated after Sunitinib treatment while upregulated in metastasis RCC tissues. Then we discovered that treating with Sunitinib, the targeted receptor tyrosine kinase inhibitor (TKI), inhibited renal cell migration and invasion via attenuating the expression of miR-452-5p. The novel identified miR-452-5p was upregulated and associated with poor prognosis in RCC. Preclinical studies using multiple RCC cells and xenografts model illustrated that miR-452-5p could promote RCC cell migration and invasion in vitro and in vivo. Mechanistically, P65 could directly bind to the miR-452-5p promoter and thus transcriptionally induce miR-452-5p expression, which led to post-transcriptionally abrogate SMAD4 expression, thus inhibition of its downstream signals including SMAD7 and EMT (Epithelial-Mesenchymal Transition) associated genes. Our study presented a road map for targeting this newly identified miR-452-5p and its SMAD4/SMAD7/EMT signals pathway, which imparted a new potential therapeutic strategy for mRCC treatment.

cancer biology↗

bioRxiv2017

High-throughput fitness profiling of Zika virus E protein reveals different roles for N-linked glycosylation during infection of mammalian and mosquito cells

Zika virus (ZIKV) infection causes Guillain-Barre syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and therefore considered one of the major determinants in ZIKV pathogenesis. Here, we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting N-linked glycosylation at N154 position display the most divergence. Through characterizing individual mutants, we show that, while ablation of N-linked glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, it either had little impact on ZIKV infection on certain human cells or decreased infection through entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.\n\nHighlightsO_LIGene-wide mapping of functional residues of E protein in human and mosquito cells.\nC_LIO_LIMutations affecting N-linked glycosylation display the most dramatic difference.\nC_LIO_LIN-linked glycosylation decreases ZIKV entry into mosquito cells.\nC_LIO_LIN-linked glycosylation is important for DC-SIGN mediated infection of human cells.\nC_LI

microbiology↗

bioRxiv2017

Exchange protein directly activated by cAMP plays a critical role in regulation of vascular fibrinolysis

RationaleTo maintain vascular patency, endothelial cells (ECs) actively regulate hemostasis. Among the myriad of pathways by which they control both fibrin formation and fibrinolysis is EC expression of annexin A2 (ANXA2) in a heterotetrameric complex with S100A10 [(ANXA2-S100A10)2]. This complex is a well-recognized endothelial surface platform for the activation of plasminogen by tissue plasminogen activator. A noteworthy advance in this field came about when it was shown that the cAMP pathway is linked to the regulation of (ANXA2-S100A10)2 in ECs.\n\nObjectiveThese findings prompted us to determine whether a druggable target, namely the exchange protein directly activated by cAMP (EPAC) pathway, plays a role in vascular luminal fibrinolysis.\n\nMethods and ResultsTaking advantage of our Epac1-null mouse model, we found that depletion of Epac1 results in fibrin deposition, fibrinolytic dysfunction, and decreased endothelial surface ANXA2 in mice, which are similar to phenomena discovered in ANXA2-null and S100A10-null mice. We observed upregulation of EPAC1 and downregulation of fibrin in endocardial tissues beneath atrial mural thrombi in humans. Of note, our thrombosis model revealed that dysfunction of fibrinolysis in EPAC1-null mice can be ameliorated by recombinant ANXA2. Furthermore, we demonstrated that suppression of EPAC1 using a small-molecule inhibitor (ESI09) reduces the expression of ANXA2 in lipid rafts and impedes ANXA2 association with S100A10. Endothelial apical surface expression of both ANXA2 and S100A10 were markedly decreased in ESI09-treated ECs, which was corroborated by results from a nanoforce spectroscopy study. Moreover, inactivation of EPAC1 decreases tyrosine 23 phosphorylation of ANXA2 in the cell membrane compartment.\n\nConclusionsOur data reveal a novel role for EPAC1 in vascular fibrinolysis, by showing that EPAC1 is responsible for the translocation of ANXA2 to the EC surface. This process promotes conversion of plasminogen to plasmin, thereby enhancing local fibrinolytic activity.

cell biology↗

bioRxiv2017

Pathogenesis of Zika Virus Infection via Rectal Route

Introduction Introduction Methods Competing interests References Zika virus (ZIKV) is a mosquito-borne flavivirus originally confined to Africa and Asia that has spread to islands located in Southeast Asia, and most recently to the Americas and the Caribbean. Approximately 80% of infected individuals are asymptomatic, while the remaining infected population exhibit mild febrile syndrome such as rash, conjunctivitis, and arthralgia. In some adults, ZIKV causes neurotropic Guillain-Barre syndrome1. Vertical transmission of ZIKV in infected mothers causes fetal growth restriction, microcephaly, and congenital eye disease2-5. Cases of ZIKV sexual transmission from male to female6-8, male to male9, ...

microbiology↗