Viscoelasticity-Controlled Relaxation in Wrinkling Surface for Multistage Time-Resolved Optical Information Encryption.

As counterfeit techniques continue to evolve, ensuring the security of conventional "static" encryption methods becomes increasingly challenging. Here, the viscoelasticity-controlled relaxation is introduced for the first time in a bilayer wrinkling system by regulating the density of hydrogen bond networks in polymer to construct a "dynamic" encryption material. The wrinkling surface can manipulate light during the dynamic relaxation process, exhibiting three stages with frosted glass, structural color, and mirror reflection. By regulating the viscoelasticity of skin layer through UV irradiation, the wavelength and the relaxation rate of the wrinkles can be controlled. As a result, dynamic wrinkling anti-counterfeiting patterns and time-resolved multistage information encryption are achieved. Crucially, the encryption material is developed as an anti-counterfeiting label for packing boxes in daily applications, allowing the encrypted information to be activated manually and identified by naked eyes, surpassing the existing time-resolved encryption materials in utilization potential. Besides, the dynamic hydrogen bond networks are extended to various dynamic interaction networks, demonstrating the versatility of the dynamic encryption strategy. This work not only provides an additional dimension for dynamic information encryption in daily practical use, but also offers theoretical guidance for the development of advanced optical anti-counterfeiting and smart display materials in the future.

CDKL1 potentiates the antitumor efficacy of radioimmunotherapy by binding to transcription factor YBX1 and blocking PD-L1 expression in lung cancer.

BACKGROUND: The evasion of the immune response by tumor cells through programmed death-ligand 1 (PD-L1) has been identified as a factor contributing to resistance to radioimmunotherapy in lung cancer patients. However, the precise molecular mechanisms underlying the regulation of PD-L1 remain incompletely understood. This study aimed to investigate the role of cyclin-dependent kinase-like 1 (CDKL1) in the modulation of PD-L1 expression and the response to radioimmunotherapy in lung cancer. METHODS: The tumorigenic roles of CDKL1 were assessed via cell growth, colony formation, and EdU assays and an in vivo nude mouse xenograft model. The in vitro radiosensitization effect of CDKL1 was evaluated using a neutral comet assay, γH2AX foci formation analysis, and a clonogenic cell survival assay. The protein‒protein interactions were confirmed via coimmunoprecipitation and GST pulldown assays. The regulation of PD-L1 by CDKL1 was evaluated via chromatin immunoprecipitation (ChIP), real-time quantitative PCR, and flow cytometry analysis. An in vitro conditioned culture model and an in vivo C57BL/6J mouse xenograft model were developed to detect the activation markers of CD8+ T cells and evaluate the efficacy of CDKL1 overexpression combined with radiotherapy (RT) and an anti-PD-L1 antibody in treating lung cancer. RESULTS: CDKL1 was downregulated and suppressed the growth and proliferation of lung cancer cells and increased radiosensitivity in vitro and in vivo. Mechanistically, CDKL1 interacted with the transcription factor YBX1 and decreased the binding affinity of YBX1 for the PD-L1 gene promoter, which consequently inhibits the expression of PD-L1, ultimately leading to the activation of CD8+ T cells and the inhibition of immune evasion in lung cancer. Moreover, the combination of CDKL1 overexpression, RT, and anti-PD-L1 antibody therapy exhibited the most potent antitumor efficacy against lung cancer. CONCLUSIONS: Our findings demonstrate that CDKL1 plays a crucial role in regulating PD-L1 expression, thereby enhancing the antitumor effects of radioimmunotherapy. These results suggest that CDKL1 may be a promising therapeutic target for the treatment of lung cancer.

MRPS16 promotes lung adenocarcinoma growth via the PI3K/AKT/Frataxin signalling axis.

Although MRPS16 is involved in cancer development, its mechanisms in developing LAUD remain unclear. Herein, qRT-PCR, WB and IHC were utilized for evaluating MRPS16 expression levels, while functional assays besides animal experiments were performed to measure MRPS16 effect on LAUD progression. Using WB, the MRPS16 effect on PI3K/AKT/Frataxin signalling pathway was tested. According to our study, MRPS16 was upregulated in LAUD and was correlated to the advanced TNM stage as well as poor clinical outcomes, which represent an independent prognostic factor. Based on functional assays, MRPS16 is involved in promoting LAUD growth, migration and invasion, which was validated further in subsequent analyses through PI3K/AKT/Frataxin pathway activation. Moreover, MRPS16-knockdown-mediated Frataxin overexpression was shown to restore the reduction in tumour cells proliferation, migration and invasion. Our results revealed that MRPS16 caused an aggressive phenotype to LAUD and was a poor prognosticator; thus, targeting MRPS16 may be effectual in LAUD treatment.

Linker-Guided Growth of Single-Crystal Covalent Organic Frameworks.

The core features of covalent organic frameworks (COFs) are crystallinity and porosity. However, the synthesis of single-crystal COFs with monomers of diverse reactivity and adjustment of their pore structures remain challenging. Here, we show that linkers that can react with a node to form single-crystal COFs can guide other linkers that form either COFs or amorphous polymers with the node to gain single-crystal COFs with mixed components, which are homogeneous on the unit cell scale with controlled ratios. With the linker-guided crystal growth method, we created nine types of single-crystal COFs with up to nine different components, which are more complex than any known crystal. The structure of the crystal adapted approximately to that of the main component, and its pore volume could be expanded up to 8.8%. Different components lead to complex and diverse pore structures and offer the possibilities to gain positive synergies, as exemplified by a bicomponent COF with 2200 and 733% SO2 uptake capacity of that of the two pure-component counterparts at 298 K and 0.002 bar. The selectivity for separation of SO2/CO2 ranges from 1230 to 4247 for flue gas based on ideal adsorbed solution theory, recording porous crystals. The bicomponent COF also exhibits a 1300% retention time of its pure-component counterparts for SO2 in a dynamic column breakthrough experiment for deep desulfurization.

Tumor-associated macrophage-derived exosomes LINC01592 induce the immune escape of esophageal cancer by decreasing MHC-I surface expression.

BACKGROUND: TAMs (tumor-associated macrophages) infiltration promotes the progression of esophageal cancer (EC). However, the underlying mechanisms remain unclear. METHODS: Abnormal expression of LINC01592 from EC microarrays of the TCGA database was analyzed. LINC01592 expression level was validated in both EC cell lines and tissues. Stable LINC01592 knockdown and overexpression of EC cell lines were established. In vitro and in vivo trials were conducted to test the impact of LINC01592 knockdown and overexpression on EC cells. RNA binding protein immunoprecipitation (RIP), RNA pulldown assays, and Immunofluorescence (IF) were used to verify the combination of E2F6 and LINC01592. The combination of E2F6 and NBR1 was verified through the utilization of ChIP and dual luciferase reporter assays. RESULTS: LINC01592 is carried and transferred by exosomes secreted by M2-TAMs to tumor cells. The molecular mechanism underlying the promotion of NBR1 transcription involves the direct binding of LINC01592 to E2F6, which facilitates the nuclear entry of E2F6. The collaborative action of LINC01592 and E2F6 results in improved NBR1 transcription. The elevation of NBR1 binding to the ubiquitinated protein MHC-I via the ubiquitin domain caused a higher degradation of MHC-I in autophagolysosomes and a reduction in MHC-I expression on the exterior of cancerous cell. Consequently, this caused cancerous cells to escape from CD8+ CTL immune attack. The tumor-promoting impacts of LINC01592, as well as the growth of M2-type macrophage-driven tumors, were significantly suppressed by the interruption of E2F6/NBR1/MHC-I signaling through the effect of siRNA or the corresponding antibody blockade. Significantly, the suppression of LINC01592 resulted in an upregulation of MHC-I expression on the tumor cell membrane, thereby enhancing the efficacy of CD8+ T cell reinfusion therapy. CONCLUSIONS: The investigation conducted has revealed a significant molecular interaction between TAMs and EC via the LINC01592/E2F6/NBR1/MHC-I axis, which facilitates the progression of malignant tumors. This suggests that a therapeutic intervention targeting this axis may hold promise for the treatment of the disease.

Growth and Local Structures of Single Crystalline Flakes of Three-Dimensional Covalent Organic Frameworks in Water.

Due to the enormous chemical and structural diversities and designable properties and functionalities, covalent organic frameworks (COFs) hold great promise as tailored materials for industrial applications in electronics, biology, and energy technologies. They were typically obtained as partially crystalline materials, although a few single-crystal three-dimensional (3D) COFs have been obtained recently with structures probed by diffraction techniques. However, it remains challenging to grow single-crystal COFs with controlled morphology and to elucidate the local structures of 3D COFs, imposing severe limitations on the applications and understanding of the local structure-property correlations. Herein, we develop a method for designed growth of five types of single crystalline flakes of 3D COFs with controlled morphology, front crystal facets, and defined edge structures as well as surface chemistry using surfactants that can be self-assembled into layered structures to confine crystal growth in water. The flakes enable direct observation of local structures including monomer units, pore structure, edge structure, grain boundary, and lattice distortion of 3D COFs as well as gradually curved surfaces in kinked but single crystalline 3D COFs with a resolution of up to ∼1.7 Å. In comparison with flakes of two-dimensional crystals, the synthesized flakes show much higher chemical, mechanical, and thermal stability.

Acteoside inhibits high glucose-induced oxidative stress injury in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway.

Diabetes retinopathy (DR) is one of the most common microvascular complications of diabetes. Retinal pigment epithelial (RPE) cells exposed to a high glucose environment experience a series of functional damages, which is an important factor in promoting the progression of DR. Acteoside (ACT) has strong antioxidant and anti-apoptotic properties, but the mechanism of ACT in DR is not completely clear. Therefore, the purpose of the present study was to explore whether ACT inhibits the damage to RPE cells in a high glucose environment through antioxidative effects to alleviate the DR process. The DR in vitro cell model was constructed by treating RPE cells with high glucose, and the DR in vivo animal model was constructed by injecting streptozotocin (STZ) into the peritoneal cavity of mice to induce diabetes. The proliferation and apoptosis of RPE cells were detected by CCK-8 and flow cytometry assays, respectively. The expression changes in Nrf2, Keap1, NQO1 and HO-1 were evaluated by qRT‒PCR, Western blot and immunohistochemistry analyses. The MDA, SOD, GSH-Px and T-AOC contents were detected by kits. The changes in ROS and nuclear translocation of Nrf2 were observed by immunofluorescence assays. HE staining was used to measure the thickness of the outer nuclear layer (ONL) of the retina, and TUNEL staining was used to detect the number of apoptotic cells in the retinas of mice. In the present study, ACT effectively ameliorated outer retina damage in diabetic mice. In high glucose (HG)-induced RPE cells, ACT treatment had the following effects: improved proliferation, decreased apoptosis, inhibited Keap1 expression, promoted the nuclear translocation and expression of Nrf2, upregulated NQO1 and HO-1 (the target genes of Nrf2) expression, decreased ROS concentration, and increased the levels of the SOD, GSH-Px and T-AOC antioxidant indicators. However, knockdown of Nrf2 reversed the above phenomena, which indicated that the protective function of ACT in HG-induced RPE cells are closely related to Nrf2. In summary, the present study demonstrated that HG-induced oxidative stress injury is inhibited by ACT in RPE cells and the outer retina through the Keap1/Nrf2/ARE pathway.

Growth of single-crystal imine-linked covalent organic frameworks using amphiphilic amino-acid derivatives in water.

A core feature of covalent organic frameworks (COFs) is crystallinity, but current crystallization processes rely substantially on trial and error, chemical intuition and large-scale screening, which typically require harsh conditions and low levels of supersaturation, hampering the controlled synthesis of single-crystal COFs, particularly on large scales. Here we report a strategy to produce single-crystal imine-linked COFs in aqueous solutions under ambient conditions using amphiphilic amino-acid derivatives with long hydrophobic chains. We propose that these amphiphilic molecules self-assemble into micelles that serve as dynamic barriers to separate monomers in aqueous solution (nodes) and hydrophobic compartments of the micelles (linkers), thereby regulating the polymerization and crystallization processes. Disordered polyimines were obtained in the micelle, which were then converted into crystals in a step-by-step fashion. Five different three-dimensional COFs and a two-dimensional COF were obtained as single crystals on the gram scale, with yields of 92% and above.

ADSC-Exos outperform BMSC-Exos in alleviating hydrostatic pressure-induced injury to retinal ganglion cells by upregulating nerve growth factors.

BACKGROUND: Mesenchymal stem cells (MSCs) have protective effects on the cornea, lacrimal gland, retina, and photoreceptor cell damage, which may be mediated by exosomes (exos) released by MSCs. AIM: To investigate the ameliorating effect of exos derived from different MSCs on retinal ganglion cell (RGC) injury induced by hydrostatic pressure. METHODS: The RGC injury model was constructed by RGC damage under different hydrostatic pressures (40, 80, 120 mmHg). Then RGCs were cultured with adipose-derived stem cell (ADSC)-Exos and bone marrow-derived stem cell (BMSC)-Exos. Cell Counting Kit-8, transmission electron microscopy, flow cytometry, immunofluorescence, real-time quantitative polymerase chain reaction, and western blotting were performed to detect the ameliorating effect of exos on pressure-induced RGC injury. RESULTS: ADSC-Exos and BMSC-Exos were successfully isolated and obtained. The gibbosity of RGCs was lower, the cells were irregularly ellipsoidal under pressure, and the addition of ADSC-Exos and BMSC-Exos significantly restored RGC morphology. Furthermore, the proliferative activity of RGCs was increased and the apoptosis of RGCs was inhibited. Moreover, the levels of lactate dehydrogenase and apoptosis-related proteins were increased, and the concentrations of antiapoptotic proteins and neurotrophic factors were decreased in damaged RGCs. However, the above indicators were significantly improved after ADSC-Exos and BMSC-Exos treatment. CONCLUSION: These findings indicated that ADSC-Exos and BMSC-Exos could ameliorate RGC injury caused by hydrostatic pressure by inhibiting apoptosis and increasing the secretion of neurotrophic factors.

Optimal acceleration voltage for near-atomic resolution imaging of layer-stacked 2D polymer thin films.

Despite superb instrumental resolution in modern transmission electron microscopes (TEM), high-resolution imaging of organic two-dimensional (2D) materials is a formidable task. Here, we present that the appropriate selection of the incident electron energy plays a crucial role in reducing the gap between achievable resolution in the image and the instrumental limit. Among a broad range of electron acceleration voltages (300 kV, 200 kV, 120 kV, and 80 kV) tested, we found that the highest resolution in the HRTEM image is achieved at 120 kV, which is 1.9 Å. In two imine-based 2D polymer thin films, unexpected molecular interstitial defects were unraveled. Their structural nature is identified with the aid of quantum mechanical calculations. Furthermore, the increased image resolution and enhanced image contrast at 120 kV enabled the detection of functional groups at the pore interfaces. The experimental setup has also been employed for an amorphous organic 2D material.

Interfacially Locked Metal Aerogel Inside Porous Polymer Composite for Sensitive and Durable Flexible Piezoresistive Sensors.

Flexible pressure sensors play significant roles in wearable devices, electronic skins, and human-machine interface (HMI). However, it remains challenging to develop flexible piezoresistive sensors with outstanding comprehensive performances, especially with excellent long-term durability. Herein, a facile "interfacial locking strategy" has been developed to fabricate metal aerogel-based pressure sensors with excellent sensitivity and prominent stability. The strategy broke the bottleneck of the intrinsically poor mechanical properties of metal aerogels by grafting them on highly elastic melamine sponge with the help of a thin polydimethylsiloxane (PDMS) layer as the interface-reinforcing media. The hierarchically porous conductive structure of the ensemble offered the as-prepared flexible piezoresistive sensor with a sensitivity as high as 12 kPa-1 , a response time as fast as 85 ms, and a prominent durability over 23 000 compression cycles. The excellent comprehensive performance enables the successful application of the flexible piezoresistive sensor as two-dimensional (2D) array device as well as three-dimensional (3D) force-detecting device for real-time monitoring of HMI activities.

MMP2 and MMP9 contribute to lung ischemia-reperfusion injury via promoting pyroptosis in mice.

BACKGROUND: Lung ischemia-reperfusion injury (LIRI) is a cause of poor prognosis in several lung diseases and after lung transplantation. In LIRI, matrix metalloproteinases and pyroptosis indicators change in parallel, both of them involvement of inflammatory modulation, but it is unclear whether they are related to each other. METHODS: We analyzed the matrix metalloproteinases (MMPs) changes from RNA sequencing (RNA-Seq) data of human transplantation and rat ischemia-reperfusion lung tissues in the Group on Earth Observations (GEO) database. Then established the mouse LIRI model to validate the changes. Further, the severity of lung injury was measured after intervening the matrix metalloproteinases changes with their selective inhibitor during Lung ischemia-reperfusion. Meanwhile, lung, pyroptosis was assessed by assaying the activity of Caspase-1 and interleukin 1ß (IL-1ß) before and after intervening the matrix metalloproteinases changes. RESULTS: The RNA-Seq data revealed that matrix metallopeptidase 2 (MMP2), matrix metallopeptidase 9 (MMP9) mRNA expression was elevated both in human lung transplantation and rat lung ischemia-reperfusion tissues, consistent with the change in our mouse model. At the same time, the activity of Caspase-1 and IL-1ß were increased after LIRI. While, the lung injury was attenuated for the use of MMP2 and MMP9 selective inhibitor SB-3CT. Likewise, lung pyroptosis alleviated when treatment the mice with SB-3CT in LIRI. CONCLUSION: We conclude that MMP2 and MMP9 are involved in the process of LIRI, the mechanism of which is related to the promotion of lung pyroptosis.

Based on multiple machine learning to identify the ENO2 as diagnosis biomarkers of glaucoma.

PURPOSE: Glaucoma is a generic term of a highly different disease group of optic neuropathies, which the leading cause of irreversible vision in the world. There are few biomarkers available for clinical prediction and diagnosis, and the diagnosis of patients is mostly delayed. METHODS: Differential gene expression of transcriptome sequencing data (GSE9944 and GSE2378) for normal samples and glaucoma samples from the GEO database were analyzed. Furthermore, based on different algorithms (Logistic Regression (LR), Random Forest (RF), lasso regression (LASSO)) two diagnostic models are constructed and diagnostic markers are screened. GO and KEGG analyses revealed the possible mechanism of differential genes in the pathogenesis of glaucoma. ROC curve confirmed the effectiveness. RESULTS: LR-RF model included 3 key genes (NAMPT, ADH1C, ENO2), and the LASSO model outputted 5 genes (IFI16, RFTN1, NAMPT, ADH1C, and ENO2), both algorithms have excellent diagnostic efficiency. ROC curve confirmed that the three biomarkers ADH1C, ENO2, and NAMPT were effective in the diagnosis of glaucoma. Next, the expression analysis of the three diagnostic biomarkers in glaucoma and control samples confirmed that NAMPT and ADH1C were up-regulated in glaucoma samples, and ENO2 was down-regulated. Correlation analysis showed that ENO2 was significantly negatively correlated with ADH1C (cor = -0.865714202) and NAMPT (cor = -0.730541227). Finally, three compounds for the treatment of glaucoma were obtained in the TCMs database: acetylsalicylic acid, 7-o-methylisomucitol and scutellarin which were applied to molecular docking with the diagnostic biomarker ENO2. CONCLUSIONS: In conclusion, our research shows that ENO2, NAMPT, and ADH1C can be used as diagnostic markers for glaucoma, and ENO2 can be used as a therapeutic target.

Double Lock Label Based on Thermosensitive Polymer Hydrogels for Information Camouflage and Multilevel Encryption.

Developing extra safety encryption technologies to prevent information leakage and combat fakes is in high demand but is challenging. Herein, we propose a "double lock" strategy based on both lower critical solution temperature (LCST) and upper critical solution temperature (UCST) polymer hydrogels for information camouflage and multilevel encryption. Two types of hydrogels were synthesized by the method of random copolymerization. The number of -CO-NH2 groups in the network structure of the hydrogels changed the enthalpic or entropic thermo-responsive hydrogels, and ultimately precisely controlled their phase transition temperature. The crosslink density of the polymer hydrogels governs the diffusion kinetics, resulting in a difference in the time for their color change. The combination of multiple LCST and UCST hydrogels in one label realized information encryption and dynamic information identification in the dimensions of both time and temperature. This work is highly interesting for the fields of information encryption, anti-counterfeiting, and smart responsive materials.

Oriented Growth of Thin Films of Covalent Organic Frameworks with Large Single-Crystalline Domains on the Water Surface.

It has been a longstanding challenge to rationally synthesize thin films of organic two-dimensional (2D) crystals with large single-crystalline domains. Here, we present a general strategy for the creation of 2D crystals of covalent organic frameworks (COFs) on the water surface, assisted by a charged polymer. The morphology of the preorganized monomers underneath the charged polymer on the water surface and their diffusion were crucial for the formation of the organic 2D crystals. Thin films of 2D COFs with an average single-crystalline domain size of around 3.57 ± 2.57 µm2 have been achieved, and their lattice structure, molecular structure, and grain boundaries were identified with a resolution down to 3 Å. The swing of chain segments and lattice distortion were revealed as key factors in compensating for the misorientation between adjacent grains and facilitating error corrections at the grain boundaries, giving rise to larger single-crystalline domains. The generality of the synthesis method was further proved with three additional 2D COFs. The oriented single-crystalline domains and clear grain boundaries render the films as model materials to study the dependence of the vertical conductivity of organic 2D crystals on domain sizes and chemical structures, and significant grain boundary effects were illustrated. This study presents a breakthrough in the controlled synthesis of organic 2D crystals with structural control at the molecular level. We envisage that this work will inspire further investigation into the microstructure-intrinsic property correlation of 2D COFs and boost their application in electronics.

Arginine methyltransferase PRMT5 methylates and destabilizes Mxi1 to confer radioresistance in non-small cell lung cancer.

Radioresistance is regarded as the main cause of local recurrence and distant metastasis in non-small cell lung cancer. However, the underlying mechanisms of radioresistance remains incompletely understood. In this study, we find that the arginine methyltransferase PRMT5 interacts with and methylates Mxi1, which promotes the binding of the ß-Trcp ligase to Mxi1, facilitating the ubiquitination and degradation of Mxi1 in lung cancer. Furthermore, genetic blockade of PRMT5 impairs DNA damage repair and enhances lung cancer radiosensitivity in vitro and in vivo, and these phenotypes are partially reversed by Mxi1 silencing. More importantly, pharmacological inhibition of PRMT5 with the specific inhibitor EPZ015666 leads to extraordinary radiosensitization in vitro and in vivo in lung cancer. Altogether, our data indicate that PRMT5 methylates and destabilizes Mxi1 to confer radioresistance, suggesting that PRMT5 may be a promising radiosensitization target in non-small cell lung cancer.

MiRNA-122 Promotes Ischemia-Reperfusion Injury after Lung Transplantation via the Toll-like Receptor Signaling Pathway.

OBJECTIVE: MiRNAs have been recently implicated in the pathogenesis of ischemia-reperfusion (IR) injury. This study aimed to investigate the miRNA expression profiles in the early stages after lung transplantation (LT) and to study the involvement of the Toll-like receptor (TLR) signaling pathway in lung IR injury following LT. METHODS: We established the left LT model in mice and selected the miRNA-122 as a research target. The mice were injected with a miRNA-122-specific inhibitor, following which pathological changes in the lung tissue were studied using different lung injury indicators. In addition, we performed deep sequencing of transplanted lung tissues to identify differentially expressed (DE) miRNAs and their target genes. These target genes were used to further perform gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: A total of 12 DE miRNAs were selected, and 2476 target genes were identified. The GO enrichment analysis predicted 6063 terms, and the KEGG analysis predicted 1554 biological pathways. Compared with the control group, inhibiting the expression of miRNA-122 significantly reduced the lung injury and lung wet/dry ratio (P<0.05). In addition, the activity of myeloperoxidase and the expression levels of tumor necrosis factor-alpha and TLR2/4 were decreased (P<0.05); whereas the expression of interleukin-10 was increased (P<0.05). Furthermore, the inhibition of miRNA-122 suppressed the IR injury-induced activation of the TLR signaling pathway. CONCLUSION: Our findings showed the differential expression of several miRNAs in the early inflammatory response following LT. Of these, miRNA-122 promoted IR injury following LT, whereas its inhibition prevented IR injury in a TLR-dependent manner.

Corrigendum: LncRNA NBR2 Inhibits the Malignancy of Thyroid Cancer, Associated With Enhancing the AMPK Signaling.

[This corrects the article DOI: 10.3389/fonc.2020.00956.].

UBE3A activates the NOTCH pathway and promotes esophageal cancer progression by degradation of ZNF185.

Background: Esophageal cancer is the sixth-most common fatal malignant tumor worldwide. Little is known regarding the genetic drivers that influence targeted therapy outcomes in patients with esophageal cancer. Exploring the pathogenesis of this lethal tumor could provide clues for developing appropriate therapeutic drugs. Ubiquitin-protein ligase E3A (UBE3A) reportedly promotes or suppresses various types of malignant tumors. However, the cancer-related role of UBE3A in esophageal cancer remains unclear. Methods: The relationship of UBE3A with the clinicopathological features of pancreatic tumors was bioinformatically investigated in the TCGA dataset. The protein levels of UBE3A and ZNF185 were assessed by Western blot and immunohistochemistry. The role of UBE3A and ZNF185 in esophageal cancer growth was assessed by MTS assays, colony formation assays, and experiments in mouse xenograft models. The interaction between UBE3A and ZNF185 was investigated by co-immunoprecipitation. The relationship between UBE3A, ZNF185, and NOTCH signaling pathway was explored by Western blot and quantitative real-time PCR. Results: We found that UBE3A was upregulated in patients with esophageal cancer and enhanced the cellular progression of esophageal cancer. Moreover, we found that UBE3A degraded ZNF185 in esophageal cancer. Additionally, ZNF185 suppressed the progression of esophageal cancer by inactivating the NOTCH pathway. Conclusions: These data demonstrated that aberrant expression of UBE3A led to enhanced progression of esophageal cancer through the ZNF185/NOTCH signaling axis. Therefore, UBE3A might be an ideal therapeutic candidate for esophageal cancer.