A Renal Clearable Nano-Assembly with Förster Resonance Energy Transfer Amplified Superoxide Radical and Heat Generation to Overcome Hypoxia Resistance in Phototherapeutics.

Given that type I photosensitizers (PSs) possess a good hypoxic tolerance, developing an innovative tactic to construct type I PSs is crucially important, but remains a challenge. Herein, we present a smart molecular design strategy based on the Förster resonance energy transfer (FRET) mechanism to develop a type I photodynamic therapy (PDT) agent with an encouraging amplification effect for accurate hypoxic tumor therapy. Of note, benefiting from the FRET effect, the obtained nanostructured type I PDT agent (NanoPcSZ) with boosted light-harvesting ability not only amplifies superoxide radical (O2•-) production but also promotes heat generation upon near-infrared light irradiation. These features facilitate NanoPcSZ to realize excellent phototherapeutic response under both normal and hypoxic environments. As a result, both in vitro and in vivo experiments achieved a remarkable improvement in therapeutic efficacy via the combined effect of photothermal action and type I photoreaction. Notably, NanoPcSZ can be eliminated from organs (including the liver, lung, spleen, and kidney) apart from the tumor site and excreted through urine within 24 h of its systemic administration. In this way, the potential biotoxicity of drug accumulation can be avoided and the biosafety can be further enhanced.

A Sulfur-Bridging Sulfonate-Modified Zinc(II) Phthalocyanine Nanoliposome Possessing Hybrid Type I and Type II Photoreactions with Efficient Photodynamic Anticancer Effects.

Phthalocyanines are potentially promising photosensitizers (PSs) for photodynamic therapy (PDT), but the inherent defects such as aggregation-caused quenching effects and non-specific toxicity severely hinder their further application in PDT. Herein, we synthesized two zinc(II) phthalocyanines (PcSA and PcOA) monosubstituted with a sulphonate group in the alpha position with "O bridge" and "S bridge" as bonds and prepared a liposomal nanophotosensitizer (PcSA@Lip) by thin-film hydration method to regulate the aggregation of PcSA in the aqueous solution and enhance its tumor targeting ability. PcSA@Lip exhibited highly efficient production of superoxide radical (O2∙-) and singlet oxygen (1O2) in water under light irradiation, which were 2.6-fold and 15.4-fold higher than those of free PcSA, respectively. Furthermore, PcSA@Lip was able to accumulate selectively in tumors after intravenous injection with the fluorescence intensity ratio of tumors to livers was 4.1:1. The significant tumor inhibition effects resulted in a 98% tumor inhibition rate after PcSA@Lip was injected intravenously at an ultra-low PcSA@Lip dose (0.8 nmol g-1 PcSA) and light dose (30 J cm-2). Therefore, the liposomal PcSA@Lip is a prospective nanophotosensitizer possessing hybrid type I and type II photoreactions with efficient photodynamic anticancer effects.

Thermal effects of beam profiles on X-ray photon correlation spectroscopy at megahertz X-ray free-electron lasers.

X-ray free-electron lasers (XFELs) with megahertz repetition rates enable X-ray photon correlation spectroscopy (XPCS) studies of fast dynamics on microsecond and sub-microsecond time scales. Beam-induced sample heating is one of the central concerns in these studies, as the interval time is often insufficient for heat dissipation. Despite the great efforts devoted to this issue, few have evaluated the thermal effects of X-ray beam profiles. This work compares the effective dynamics of three common beam profiles using numerical methods. Results show that under the same fluence, the effective temperatures increase with the nonuniformity of the beam, such that the Gaussian beam profile yields a higher effective temperature than the donut-like and uniform profiles. Moreover, decreasing the beam sizes is found to reduce beam-induced thermal effects, in particular the effects of beam profiles.

lncRNA DLEU2 promotes gastric cancer progression through ETS2 via targeting miR-30a-5p.

BACKGROUND: Gastric cancer (GC) remains an important cancer worldwide. Further understanding of the molecular mechanisms of gastric carcinogenesis will enhance the diagnosis and treatment of GC. METHODS: The expression of DLEU2 and ETS2 was analyzed in several GC cell lines using GEPIA online analyze, qRT-PCR and immunohistochemistry. The biological behavior of GC cells was detected by CCK8, clone formation, transwell, wound healing, western blot, and flow cytometry assay. More in-depth mechanisms were studied. RESULTS: DLEU2 was significantly up-regulated in GC tissues and cell lines. The expression of DLEU2 was significantly associated with pathological grading and TNM stage of GC patients. Furthermore, knockdown of DLEU2 inhibited the proliferation, migration, and invasion of AGS and MKN-45 cells, while overexpression of DLEU2 promoted the proliferation, migration, and invasion of HGC-27 cells. MiR-30a-5p could directly bind to the 3' UTR region of ETS2. Moreover, DLEU2 bound to miR-30a-5p through the same binding site, which facilitated the expression of ETS2. Knockdown of DLEU2 reduced the protein level of intracellular ETS2 and inhibited AKT phosphorylation, while overexpression of DLEU2 induced the expression of ETS2 and the phosphorylation of AKT. ETS2 was highly expressed in GC tissues. The expression of ETS2 was significantly associated with age, pathological grading, and TNM stage. ETS2 overexpression promoted cell proliferation and migration of AGS and MKN-45 cells. Furthermore, ETS2 overexpression rescued cell proliferation and migration inhibition induced by DLEU2 down-regulation and miR-30a-5p up-regulation in AGS and MKN-45 cells. CONCLUSIONS: DLEU2 is a potential molecular target for GC treatment.

A pediatric case of generalized lichen aureus.

Lichen aureus is a particularly rare subtype of pigmented purpuric dermatosis and is characterized by the sudden appearance of golden or rust-colored macules or needle-tip-sized flat papules (concentrated in one region to form lichenoid papules) on the lower limbs. These skin lesions are usually confined to an isolated, unilateral distribution, and linear segmental distribution is rare. In this report, we have documented one such case, where the lesions on the limb were arranged in strips (segmental distribution) that roughly followed the direction of the venous drainage. And the first attack and subsequent aggravation were both associated with the onset of allergic rhinitis, a Type I hypersensitivity.

Overexpression of CD59 inhibits apoptosis of T-acute lymphoblastic leukemia via AKT/Notch1 signaling pathway.

BACKGROUND: T-acute lymphoblastic leukemia (T-ALL) was a hematological malignancy characterized by the accumulation of immature T cells in bone marrow and peripheral blood. In this study, we tried to explore the physiological role of CD59 in T-ALL. METHODS: In this study, we collected the bone marrow samples from 17 T-ALL patients and 38 healthy participants to find differences in CD59 expression patterns. Then, CD59 was over-expressed in T-ALL cell line Jurkat, and its biological functions were detected. In addition, in order to understand the active site of CD59, the Trp40 was mutated. Further, we constructed a mouse model by transplanting Jurkat cells into the nude mice to verify the function of CD59 in vitro. At last, mechanism studies were performed by western blot. RESULTS: We found that the proportion of T lymphocytes expressing CD59 in bone marrow of T-ALL patients was significantly higher than that of healthy individuals. Then, we found that the overexpression of CD59 in Jurkat cells was beneficial to the cell survival by inhibiting apoptosis and promoting IL-2 secretion. In this process, Trp40 of CD59 was a key functional site. Further, the high expression of CD59 inhibited apoptosis of bone marrow and peripheral blood cells, and promoted IL-2 secretion in mouse model. At last, mechanism studies showed that the activation of AKT, STAT5 and Notch1 signaling pathways in Jurkat cells, may be involved in the regulation of apoptosis by CD59; and mutation in the Trp40 affect the interaction of CD59 with these signaling pathways. CONCLUSIONS: In conclusion, CD59 inhibited apoptosis of T-ALL by regulating AKT/Notch1 signaling pathway, providing a new perspective for the treatment of T-ALL.

Novel Pattern Recognition Receptor Protects Shrimp by Preventing Bacterial Colonization and Promoting Phagocytosis.

The recognition of pathogen-associated molecular patterns is accomplished by the recognition modules of pattern recognition receptors (PRRs). Leucine-rich repeats (LRRs) and C-type lectin-like domain (CTLD) represent the two most universal categories of recognition modules. In the current study, we identified a novel soluble and bacteria-inducible PRR comprising LRRs and a CTLD from the hepatopancreas of kuruma shrimp Marsupenaeus japonicus and named it Leulectin. The module arrangement of Leulectin is unique among all organisms. Both modules, together with the whole molecule, protected shrimp against Vibrio infection. By screening the pathogen-associated molecular patterns that shrimp might encounter, Leulectin was found to sense Vibrio flagellin through the LRRs and to recognize LPS through CTLD. The LRR-flagellin interaction was confirmed by pull-down and far-Western assays and was found to rely on the fourth LRR of Leulectin and the N terminus of flagellin. The recognition of LPS was determined by the long loop region of CTLD in a calcium-independent manner. By sensing the flagellin, LRRs could prevent its attachment to shrimp cells, thereby inhibiting Vibrio colonization. With the ability to recognize LPS, CTLD could agglutinate the bacteria and promote hemocytic phagocytosis. Our study clearly showed the division of labor and the synergy between different recognition modules and provided new insights into the concept of pattern recognition and the function of soluble PRRs in the antibacterial response.

Vesicle Adhesion and Fusion Studied by Small-Angle X-Ray Scattering.

We have studied the adhesion state (also denoted by docking state) of lipid vesicles as induced by the divalent ions Ca2+ or Mg2+ at well-controlled ion concentration, lipid composition, and charge density. The bilayer structure and the interbilayer distance in the docking state were analyzed by small-angle x-ray scattering. A strong adhesion state was observed for DOPC:DOPS vesicles, indicating like-charge attraction resulting from ion correlations. The observed interbilayer separations of ∼1.6 nm agree quantitatively with the predictions of electrostatics in the strong coupling regime. Although this phenomenon was observed when mixing anionic and zwitterionic (or neutral) lipids, pure anionic membranes (DOPS) with highest charge density σ resulted in a direct phase transition to a multilamellar state, which must be accompanied by rupture and fusion of vesicles. To extend the structural assay toward protein-controlled docking and fusion, we have characterized reconstituted N-ethylmaleimide-sensitive factor attachment protein receptors in controlled proteoliposome suspensions by small-angle x-ray scattering.

Reconstitution of SNARE proteins into solid-supported lipid bilayer stacks and X-ray structure analysis.

SNAREs are known as an important family of proteins mediating vesicle fusion. For various biophysical studies, they have been reconstituted into supported single bilayers via proteoliposome adsorption and rupture. In this study we extended this method to the reconstitution of SNAREs into supported multilamellar lipid membranes, i.e. oriented multibilayer stacks, as an ideal model system for X-ray structure analysis (X-ray reflectivity and diffraction). The reconstitution was implemented through a pathway of proteomicelle, proteoliposome and multibilayer. To monitor the structural evolution in each step, we used small-angle X-ray scattering for the proteomicelles and proteoliposomes, followed by X-ray reflectivity and grazing-incidence small-angle scattering for the multibilayers. Results show that SNAREs can be successfully reconstituted into supported multibilayers, with high enough orientational alignment for the application of surface sensitive X-ray characterizations. Based on this protocol, we then investigated the effect of SNAREs on the structure and phase diagram of the lipid membranes. Beyond this application, this reconstitution protocol could also be useful for X-ray analysis of many further membrane proteins.

Identification of a crustacean ß-1,3-glucanase related protein as a pattern recognition protein in antibacterial response.

Prophenoloxidase (proPO) activating system is an important immune response for arthropods. ß-1, 3-glucanase related protein (previously named as lipopolysaccharide and ß-1, 3-glucan binding protein (LGBP) in crustaceans) is a typical pattern recognition receptor family involved in the proPO activation by recognizing the invading microbes. In this study, we pay special attention to a bacteria-induced ß-1,3-glucanase related protein from red swamp crayfish Procambarus clarkii, an important aquaculture specie in China. This protein, designated PcBGRP, was found a typical member of crustacean BGRP family with the glucanase-related domain and the characteristic motifs. PcBGRP was expressed in hemcoyes and hepatopancreas, and its expression could be induced by the carbohydrate and bacteria stimulants. The induction by lipopolysaccharide (LPS) and ß-1,3-glucan (ßG) was more significant than by peptidoglycan (PG). The response of PcBGRP to the native Gram-negative bacterial pathogen Aeromonas hydrophila was more obvious than to Gram-positive bacteria. Using RNA interference and recombinant protein, PcBGRP was found to protect crayfish from A. hydrophila infection revealed by the survival test and morphological analysis. A mechanism study found PcBGRP could bind LPS and ßG in a dose-dependent manner, and the LPS recognizing ability determined the Gram-negative bacterium binding activity of PcBGRP. PcBGRP was found to enhance the PO activation both in vitro and in vivo, and the protective role was related to the PO activating ability of PcBGRP. This study emphasized the role of BGRP family in crustacean immune response, and provided new insight to the immunity of red swamp crayfish which suffered serious disease during the aquaculture in China.

Association Study Confirmed Three Breast Cancer-Specific Molecular Subtype-Associated Susceptibility Loci in Chinese Han Women.

BACKGROUND: Breast cancer is a heterogeneous and polygenic disease that can be divided into different molecular subtypes based on histological and genomic features. To date, numerous susceptibility loci of breast cancer have been discovered by genome-wide association studies and may expand the genetic features. However, few loci have been further studied according to molecular subtypes. MATERIALS AND METHODS: We genotyped 23 recently discovered single nucleotide polymorphisms using the Sequenom iPLEX platform in a female Chinese cohort of 3,036 breast cancer patients (2,935 samples matched molecular subtypes) and 3,036 healthy controls. RESULTS: Through a stratification analysis, 5q11.2/MAP3K1 (rs16886034, rs16886364, rs16886397, rs1017226, rs16886448) and 7q32.3/LINC-PINT (rs4593472) were associated with Luminal A, and 10q26.1/FGFR2 (rs35054928) was associated with Luminal B. CONCLUSION: In our study, breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes. IMPLICATIONS FOR PRACTICE: To date, genome-wide association studies have identified more than 90 susceptibility loci associated with breast cancer. However, few loci have been further studied according to molecular subtype. The results of this study are that breast cancer-specific molecular subtype-associated susceptibility loci were confirmed in Chinese Han women, which contributes to a better genetic understanding of breast cancer in different molecular subtypes.

Stalk formation as a function of lipid composition studied by X-ray reflectivity.

We have investigated the structure and interaction of solid-supported multilamellar phospholipid bilayers in view of stalk formation as model systems for membrane fusion. The multi-component bilayers were composed of ternary and quaternary mixtures, containing phosphatidylcholines, phosphatidylethanolamines, sphingomyelin, cholesterol, diacylglycerol, and phosphatidylinositol. Analysis of the obtained electron density profiles and the pressure-distance curves reveals systematic changes in structure and hydration repulsion. The osmotic pressure needed to induce stalk formation at the transition from the fluid lamellar to the rhombohedral phase indicates how membrane fusion properties are modified by bilayer composition.

Association study confirms two susceptibility loci for breast cancer in Chinese Han women.

To date, many loci associated with breast cancer have been identified through genome-wide association studies; most of these studies were conducted using populations of European descent. Thus, it is not clear whether these susceptibility loci are also risk factors for Chinese populations. We selected and genotyped 32 single nucleotide polymorphisms (SNPs) using the Sequenom iPLEX platform in a female Chinese cohort of 3036 breast cancer cases and 3036 healthy controls. A total of 23 SNPs passed the quality control test. The associations of these SNPs with disease susceptibility were assessed using logistic regression, adjusting for age. The Bonferroni correction was used to conservatively account for multiple testing, and the threshold for statistical significance was P < 2.17 × 10(-3) (0.05/23). We confirmed ten risk-associated variants within three reported breast cancer susceptibility loci in a Chinese Han population: 5q11.2 (rs16886181, P = 5.29 × 10(-6), OR = 1.19; rs1017226, P = 5.24 × 10(-4), OR = 1.22; rs16886034, P = 2.00 × 10(-3), OR = 1.21; rs16886113, P = 1.24 × 10(-3), OR = 1.20; rs16886364, P = 9.20 × 10(-4), OR = 1.21; rs16886397, P = 1.17 × 10(-3), OR = 1.20; rs16886448, P = 1.62 × 10(-3,)OR = 1.20; and rs2229882, P = 5.14 × 10(-4), OR = 1.31), 5q14.3 (rs421379, P = 2.83 × 10(-13), OR = 1.83), and 10q26.1 (rs35054928, P = 7.73 × 10(-6), OR = 1.18). The 10q26.1 locus was found to be a susceptibility locus for breast cancer in Chinese Han women in our previous studies. 5q11.2 and 5q14.3 are confirmed here for the first time as susceptibility loci for breast cancer in Chinese Han women. This study reports three breast cancer susceptibility loci that were previously identified in European populations and are also risk factors for Chinese populations. This study may extend the genetic basis of breast cancer in Chinese Han women and highlight the contribution of multiple variants of modest effect.

Heavy-Atom Labeled Transmembrane ß-Peptides: Synthesis, CD-Spectroscopy, and X-ray Diffraction Studies in Model Lipid Multilayer.

Transmembrane ß-peptides are promising candidates for the design of well-controlled membrane anchors in lipid membranes. Here, we present the synthesis of transmembrane ß-peptides with and without tryptophan anchors, as well as a novel iodine-labeled d-ß(3) -amino acid. By using one or more of the heavy-atom labeled amino acids as markers, the orientation of the helical peptide was inferred based on the electron-density profile determined by X-ray reflectivity. The ß-peptides were synthesized through manual Fmoc-based solid-phase peptide synthesis (SPPS) and reconstituted in unilamellar vesicles forming a right-handed 314 -helix secondary structure, as shown by circular dichroism spectroscopy. We then integrated the ß-peptide into solid-supported membrane stacks and carried out X-ray reflectivity and grazing incidence small-angle X-ray scattering to determine the ß-peptide orientation and its effect on the membrane bilayers. These ß-peptides adopt a well-ordered transmembrane motif in the solid-supported model membrane, maintaining the basic structure of the original bilayer with some distinct alterations. Notably, the helical tilt angle, which accommodates the positive hydrophobic mismatch, induces a tilt of the acyl chains. The tilted chains, in turn, lead to a membrane thinning effect.

Collaboration between a soluble C-type lectin and calreticulin facilitates white spot syndrome virus infection in shrimp.

White spot syndrome virus (WSSV) mainly infects crustaceans through the digestive tract. Whether C-type lectins (CLs), which are important receptors for many viruses, participate in WSSV infection in the shrimp stomach remains unknown. In this study, we orally infected kuruma shrimp Marsupenaeus japonicus to model the natural transmission of WSSV and identified a CL (designated as M. japonicus stomach virus-associated CL [MjsvCL]) that was significantly induced by virus infection in the stomach. Knockdown of MjsvCL expression by RNA interference suppressed the virus replication, whereas exogenous MjsvCL enhanced it. Further analysis by GST pull-down and coimmunoprecipitation showed that MjsvCL could bind to viral protein 28, the most abundant and functionally relevant envelope protein of WSSV. Furthermore, cell-surface calreticulin was identified as a receptor of MjsvCL, and the interaction between these proteins was a determinant for the viral infection-promoting activity of MjsvCL. The MjsvCL-calreticulin pathway facilitated virus entry likely in a cholesterol-dependent manner. This study provides insights into a mechanism by which soluble CLs capture and present virions to the cell-surface receptor to facilitate viral infection.

Structural study of MCPIP1 N-terminal conserved domain reveals a PIN-like RNase.

MCP-1-induced protein 1 (MCPIP1) plays an important role in the downregulation of the LPS-induced immune response by acting as an RNase targeting IL-6 and IL-12b mRNAs. A conserved domain located in the N-terminal part of MCPIP1 is thought to be responsible for its RNase activity, but its catalytic mechanism is not well understood due to the lack of an atomic resolution structure. We determined the 3D crystal structure of this MCPIP1 N-terminal conserved RNase domain at a resolution of 2.0 Å. The overall structure of MCPIP1 N-terminal conserved domain shares high structural homology with PilT N-terminal domain. We show that the RNase catalytic center is composed of several acidic residues, verifying their importance by site-specific mutagenesis. A positively charged arm close to the catalytic center may act as an RNA substrate-binding site, since exchange of critical positively charged residues on this arm with alanine partially abolish the RNase activity of MCPIP1 in vivo. Our structure of the MCPIP1 N-terminal conserved domain reveals the details of the catalytic center and provides a greater understanding of the RNA degradation mechanism.

Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation.

The zinc-finger antiviral protein (ZAP) was originally identified as a host factor that inhibits the replication of Moloney murine leukemia virus. Here we report that ZAP inhibits HIV-1 infection by promoting the degradation of specific viral mRNAs. Overexpression of ZAP rendered cells resistant to HIV-1 infection in a ZAP expression level-dependent manner, whereas depletion of endogenous ZAP enhanced HIV-1 infection. Both human and rat ZAP inhibited the propagation of replication-competent HIV-1. ZAP specifically targeted the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. We provide evidence indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA exosome to degrade the RNA body from the 3' end. In addition, ZAP recruits cellular decapping complex through its cofactor RNA helicase p72 to initiate degradation of the target viral mRNA from the 5' end. Depletion of each of these mRNA degradation enzymes reduced ZAP's activity. Our results indicate that ZAP inhibits HIV-1 by recruiting both the 5' and 3' mRNA degradation machinery to specifically promote the degradation of multiply spliced HIV-1 mRNAs.

Learning Optical Flow and Scene Flow With Bidirectional Camera-LiDAR Fusion.

In this paper, we study the problem of jointly estimating the optical flow and scene flow from synchronized 2D and 3D data. Previous methods either employ a complex pipeline that splits the joint task into independent stages, or fuse 2D and 3D information in an "early-fusion" or "late-fusion" manner. Such one-size-fits-all approaches suffer from a dilemma of failing to fully utilize the characteristic of each modality or to maximize the inter-modality complementarity. To address the problem, we propose a novel end-to-end framework, which consists of 2D and 3D branches with multiple bidirectional fusion connections between them in specific layers. Different from previous work, we apply a point-based 3D branch to extract the LiDAR features, as it preserves the geometric structure of point clouds. To fuse dense image features and sparse point features, we propose a learnable operator named bidirectional camera-LiDAR fusion module (Bi-CLFM). We instantiate two types of the bidirectional fusion pipeline, one based on the pyramidal coarse-to-fine architecture (dubbed CamLiPWC), and the other one based on the recurrent all-pairs field transforms (dubbed CamLiRAFT). On FlyingThings3D, both CamLiPWC and CamLiRAFT surpass all existing methods and achieve up to a 47.9% reduction in 3D end-point-error from the best published result. Our best-performing model, CamLiRAFT, achieves an error of 4.26% on the KITTI Scene Flow benchmark, ranking 1st among all submissions with much fewer parameters. Besides, our methods have strong generalization performance and the ability to handle non-rigid motion.

Serum iron level is independently associated with sarcopenia: a retrospective study.

Sarcopenia greatly reduces the quality of life of the elderly, and iron metabolism plays an important role in muscle loss. This study aimed to investigate the association between iron status and sarcopenia. A total of 286 adult patients hospitalized between 2019 and 2021 were included in this study, of which 117 were diagnosed with sarcopenia. Serum iron, total iron binding capacity (TIBC), transferrin, and transferrin saturation levels were compared between groups with and without sarcopenia and were included in the logistic analyses, with significant variables further included in the logistic regression model for the prediction of sarcopenia. Serum iron, TIBC, and transferrin levels decreased significantly in the sarcopenia group (p < 0.05), and were negatively associated with handgrip strength, relative skeletal muscle index, and multiple test performances (p < 0.05). Multivariate logistic analysis showed that sex, age, body mass index (BMI), and serum iron level were independent risk factors for sarcopenia. In the final logistic regression model, male sex (odds ratio [OR] 3.65, 95% confidence interval [CI] 1.67-7.98), age > 65 years (OR 5.40, 95% CI 2.25-12.95), BMI < 24 kg/m2 (OR 0.17, 95% CI 0.08-0.36), and serum iron < 10.95 µmol/L (OR 0.39, 95% CI 0.16-0.93) were included. Our study supported the impact of iron metabolism on muscle strength and performance.

HIF-1α contributes to metastasis in choriocarcinoma by regulating DEC1 expression.

PURPOSE: To elucidate the underlying mechanism of HIF-1α in migration and invasion of choriocarcinoma. METHODS: Cell proliferation was determined by CCK-8 assay when cell invasion was detected by transwell assay. The protein expression was detected by western blotting, immunohistochemistry, and qPCR assay. RESULT: HIF-1α was shown to be strongly expressed in both clinical tumour tissues and cell lines in choriocarcinoma. When HIF-1α was efficiently knocked down in JEG3 cells, the proliferation rate was reduced by approximately 50% and the number of cells that migrated through the transwell insert was greatly decreased. The cell invasion rate was also significantly reduced. Moreover, typical markers of epithelial-mesenchymal transition such as E-cadherin, were increased, while vimentin and α-SMA were decreased after HIF-1α knockdown. In contrast, overexpression of DEC1 reversed the effects of HIF-1α knockdown. Cell proliferation, migration, and invasion were partially recovered. The level of E-cadherin was decreased, while the level of vimentin and α-SMA was increased. In addition, the level of ß-catenin and LEF1 was downregulated after HIF-1α knockdown. The expression of MMP2 and MMP9 also declined. However, overexpression of DEC1 after HIF-1α knockdown partially reversed the expression pattern of these molecules. CONCLUSION: HIF-1α contributed to EMT and metastasis through activation of canonical ß-catenin signalling in choriocarcinoma and this process was dependent on DEC1. This study provides a new mechanism of HIF-1α in choriocarcinoma and suggests that intervention with DEC1 might be a promising therapeutic choice for choriocarcinoma.