Cation vacancy-boosted BaZnB4O8:xEu3+ phosphors with high quantum yield and thermal stability for pc-WLEDs.

Achieving high luminescent quantum yield and thermal stability of phosphors simultaneously remains challenging, yet it is critical for facilitating high-power white light emitting diodes (WLEDs). Herein, we report the design and preparation of the layered structure BaZnB4O8:xEu3+ (0.10 ≤ x ≤ 0.60) red phosphors with high quantum yield (QY = 76.5%) and thermal stability (82.8%@150 °C) by the traditional solid-state reaction method. The results of XRD and Rietveld refinement show that the presence of Eu3+ ions at Ba2+ sites causes the formation of cation (Zn2+/Ba2+) vacancies in the lattice. The PL and PL decay results reveal that the quenching concentration of BZBO:xEu3+ phosphors is as high as 50%, and the lifetime remains unchanged with Eu3+ concentration due to the unique structure of the host and the cation vacancies generated by the heterovalent substitution. Furthermore, on a 395 nm near-UV chip, a pc-WLED device with exceptional optical performance (CCT = 4415 K, CRI = 92.1) was realized using the prepared BZBO:0.50Eu3+ as a red phosphor. Simple synthesis and excellent performance parameters suggest that the reported BaZnB4O8:xEu3+ phosphors have promising applications in high-power pc-WLEDs. At the same time, it also indicates that cationic vacancy engineering based on heterovalent ion substitution is a potential strategy for improving luminescence quantum yield and thermal quenching performance.

Genome-wide identification and expression analyses of Toll-like receptors provide new insights on adaptation to intertidal benthic environments in Urechis unicinctus (Annelida, Echiura).

Toll-like receptors (TLR) are an important class of pattern recognition receptors involved in innate immunity that recognize pathogen-associated and damage-associated molecular patterns. Although the role of TLRs in immunity has been extensively studied, a systematic investigation of their function in environmental adaptation is still in its infancy. In this study, a genome-wide search was conducted to systematically investigate TLR family members of Urechis unicinctus, a typical benthic organism in intertidal mudflats. A total of 28 TLR genes were identified in the U. unicinctus genome, and their fundamental physiological and biochemical properties were characterized. Gene copy number analysis among species in different habitats indicated that TLR family gene expansion may be probably related with benthic environmental adaptation. To further investigate the expression patterns of TLR members under environmental stress, transcriptome data was analyzed from different developmental stages and the hindgut under sulfide stress. Transcriptome analysis of different developmental stages showed that most TLR genes were highly expressed during a key period of benthic environment adaptation (worm-shaped larva). Transcriptome analysis of the hindgut under sulfide stress showed that the expression of 12 TLR members was significantly induced under sulfide stress. These results indicate that the regulation of TLR gene expression may be probably involved in the adaptation of U. unicinctus to the benthic intertidal zone environment. Taken together, this study may lay the foundation for future functional analysis of the specific role of TLRs in host immune responses against sulfide exposure and benthic environmental stress in annelid.

Identification and validation of the reference genes in the echiuran worm Urechis unicinctus based on transcriptome data.

BACKGROUND: Real-time quantitative PCR (RT-qPCR) is a crucial and widely used method for gene expression analysis. Selecting suitable reference genes is extremely important for the accuracy of RT-qPCR results. Commonly used reference genes are not always stable in various organisms or under different environmental conditions. With the increasing application of high-throughput sequencing, transcriptome analysis has become an effective method for identifying novel stable reference genes. RESULTS: In this study, we identified candidate reference genes based on transcriptome data covering embryos and larvae of early development, normal adult tissues, and the hindgut under sulfide stress using the coefficient of variation (CV) method in the echiuran Urechis unicinctus, resulting in 6834 (15.82%), 7110 (16.85%) and 13880 (35.87%) candidate reference genes, respectively. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the candidate reference genes were significantly enriched in cellular metabolic process, protein metabolic process and ribosome in early development and normal adult tissues as well as in cellular localization and endocytosis in the hindgut under sulfide stress. Subsequently, ten genes including five new candidate reference genes and five commonly used reference genes, were validated by RT-qPCR. The expression stability of the ten genes was analyzed using four methods (geNorm, NormFinder, BestKeeper, and ∆Ct). The comprehensive results indicated that the new candidate reference genes were more stable than most commonly used reference genes. The commonly used ACTB was the most unstable gene. The candidate reference genes STX12, EHMT1, and LYAG were the most stable genes in early development, normal adult tissues, and hindgut under sulfide stress, respectively. The log2(TPM) of the transcriptome data was significantly negatively correlated with the Ct values of RT-qPCR (Ct = - 0.5405 log2(TPM) + 34.51), which made it possible to estimate the Ct value before RT-qPCR using transcriptome data. CONCLUSION: Our study is the first to select reference genes for RT-qPCR from transcriptome data in Echiura and provides important information for future gene expression studies in U. unicinctus.

Synthesis, Photoluminescent Characteristics and Eu3+-Induced Phase Transitions in Sr3Zr2O7:Eu3+ Red Phosphors.

Designing phosphors that are excited by blue light is extraordinarily important for white light-emitting diodes (w-LEDs). In the present study, a new Ruddlesden-Popper type of SZO:xEu3+ (x = 0.01~0.10) phosphors was developed using solid-state reactions. Interestingly, a Eu3+ doping-induced phase transformation from the Sr3Zr2O7 (cubic) to the SrZrO3 (orthorhombic) phase was observed, and the impact of the occupied sites of Eu3+ ions on the lifetime of Sr3Zr2O7:xEu3+ phosphors is discussed in detail. Diffuse reflectance spectroscopy results showed that the band gap of SZO:xEu3+ phosphors gradually increased from 3.48 eV for undoped Sr3Zr2O7 hosts to 3.67 eV for SZO:0.10Eu3+ samples. The fluorescence excitation spectrum showed that ultraviolet (300 nm), near-ultraviolet (396 nm) and blue light (464 nm) were all effective excitation pump sources of Sr3Zr2O7:xEu3+ phosphors, and the strongest emission at 615 nm originated from an electric dipole transition (5D0→7F2). CIE coordinates moved from orange (0.5969, 0.4267) to the reddish-orange region (0.6155, 0.3827), and the color purity also increased. The fabricated w-LED was placed on a 460 nm chip with a mixture of YAG:Ce3+ and SZO:0.1Eu3+ samples and showed "warm" white light with a color rendering index (CRI) of 81.8 and a correlation color temperature (CCT) of 5386 K, indicating great potential for application in blue chip white LEDs.

Nanoparticles loaded with circ_0086375 for suppressing the tumorigenesis of pancreatic cancer by targeting the miR-646/SLC4A4 axis.

Nanoparticles possess the ability to adsorb and load other compounds. This study aimed to synthesize a gene carrier with polyethyleneimine (PEI), hyaluronic acid (HA) and mesoporous silica nanoparticles (MSNs) for circ_0086375 delivery to investigate the role and mechanism of circ_0086375 in pancreatic cancer (PC) progression. The expression of genes and proteins was detected by quantitative real-time polymerase chain reaction and Western blot. In vitro experiments were performed by cell counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, transwell assay, and wound healing assay, respectively. Dual-luciferase activity assay was used to investigate the target relationship between miR-646 and circ_0086375 or SLC4A4 (solute carrier family 4 member 4). Circ_0086375 loaded PEI/HA-based mesoporous silica nanoparticles (MSNs) were prepared, and in vivo assay was performed by using xenograft tumor model. Circ_0086375 expression was decreased in PC tissues and cells. Restoration of circ_0086375 suppressed PC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, circ_0086375 acted as a sponge for miR-646 to elevate SLC4A4 expression, which was confirmed to be a target of miR-646. The prepared circ_0086375/MSN/PEI/HA nanocomplexes showed excellent fluorescent properties and a higher cellular uptake of circ_0086375 in PC cells. Moreover, circ_0086375/MSN/PEI/HA showed relatively more anticancer effects in PC than that of circ_0086375 alone in vitro and in vivo. Delivery of circ_0086375 by nanoparticles suppresses the tumorigenicity of pancreatic cancer by miR-646/SLC4A4 axis, suggesting a new potential target for future pancreatic cancer treatment.

Anti­silencing function 1B promotes the progression of pancreatic cancer by activating c­Myc.

The present study aimed to explore the role of histone chaperone anti­silencing function 1B (ASF1B) in pancreatic cancer and the underlying mechanism. The biological function of ASF1B was investigated in pancreatic cancer cell lines (PANC­1 and SW1990) and a mouse xenograft model. Chromatin immunoprecipitation was used to detect the effect of ASF1B on the transcriptional activity of c­Myc. ASF1B was highly expressed in pancreatic adenocarcinoma (PAAD) samples from The Cancer Genome Atlas. ASF1B expression was positively associated with poor survival rates in patients with PAAD. Silencing of ASF1B in PANC­1 and SW1990 cells inhibited cell proliferation, migration and invasion, and induced apoptosis. Mechanistically, ASF1B increased H3K56 acetylation (H3K56ac) in a CREB­binding protein (CBP)­dependent manner. ASF1B promoted H3K56ac at the c­Myc promoter and increased c­Myc expression. In PANC­1 and SW1990 cells, the CBP inhibitor curcumin and the c­Myc inhibitor 10058­F4 reversed the promoting effects of ASF1B on cell proliferation, migration and invasion. In the mouse xenograft model, ASF1B silencing inhibited tumor growth, and was associated with low H3K56ac and c­Myc expression. ASF1B promoted pancreatic cancer progression by activating c­Myc via CBP­mediated H3K56ac.

Association of hepatitis B virus DNA levels with overall survival for advanced hepatitis B virus-related hepatocellular carcinoma under immune checkpoint inhibitor therapy.

BACKGROUND: High hepatitis B virus (HBV) DNA level is an independent risk factor for postoperative HBV-associated liver cancer recurrence. We sought to examine whether HBV DNA level and antiviral therapy are associated with survival outcomes in patients with advanced hepatocellular carcinoma (HCC) treated with anti-programmed cell death protein 1 (PD-1)based immunotherapy. METHODS: This single-institution retrospective analysis included 217 patients with advanced HBV-related HCC treated from 1 June 2018, through 30 December 2020. Baseline information was compared between patients with low and high HBV DNA levels. Overall survival (OS) and progression-free survival (PFS) were compared, and univariate and multivariate analyses were applied to identify potential risk factors for oncologic outcomes. RESULTS: The 217 patients included in the analysis had a median survival time of 20.6 months. Of these HBV-associated HCC patients, 165 had known baseline HBV DNA levels. Baseline HBV DNA level was not significantly associated with OS (P = 0.59) or PFS (P = 0.098). Compared to patients who did not receive antiviral therapy, patients who received antiviral therapy had significantly better OS (20.6 vs 11.1 months, P = 0.020), regardless of HBV DNA levels. Moreover, antiviral status (adjusted HR = 0.24, 95% CI 0.094-0.63, P = 0.004) was an independent protective factor for OS in a multivariate analysis of patients with HBV-related HCC. CONCLUSIONS: HBV viral load does not compromise the clinical outcome of patients with HBV-related HCC treated with anti-PD-1-based immunotherapy. The use of antiviral therapy significantly improves survival time of HBV-related HCC patients.

HKUST-1 nano metal-organic frameworks combined with ZnGa2O4:Cr3+ near-infrared persistent luminescence nanoparticles for in vivo imaging and tumor chemodynamic and photothermal synergic therapy.

The multifunctional theranostic nanoplatform based on the combination of persistent luminescent nanoparticles (PLNPs) and metal-organic frameworks (MOFs) has both in vivo imaging and tumor therapeutic drug-loading functions, providing a new strategy for accurate and effective tumor diagnosis and treatment. Herein, the near-infrared (NIR) PLNP SiO2@Zn1.05Ga1.9O4:Cr was combined with HKUST-1 MOFs to form a core-shell structure theranostic nanoplatform which possessed the triple function of autofluorescence-free NIR PersL bioimaging, tumor chemodynamic therapy (CDT), and tumor photothermal therapy (PTT). Also, the photothermal conversion efficiency reached 58.7%, which is superior to the reported nano metal-organic framework (NMOF) photothermal reagents. We demonstrated that the nanoplatform could enter the tumors of mice within 0.5 h and could be target-activated by H2O2 and H2S in the tumor cells, resulting in effective PTT and CDT synergistic treatment. Tumor-bearing mice experiments showed that the tumor could be completely cured without harming normal tissue. This theranostic nanoplatform may provide a promising strategy showing imaging, PTT, and CDT synergistic treatment tri-mode for clinical cancer therapy.

Charge compensation engineering for high-performance dolomite-type BaTi(BO3)2:Eu3+ red-emitting phosphor for backlight display applications with a wide color gamut.

Exploiting high color purity phosphors is a core problem in the development of phosphor conversion light-emitting diodes (pc-LEDs) for display devices. Eu3+-activated BaTi(BO3)2 (BTB) red-emitting phosphors were first synthesized via a solid-state reaction at low temperature and alkali metal ions Na+ were co-doped in BTB:xEu3+ to improve the luminescence properties. The occupation of the Eu3+ ions and the enhancement principles of the Na+ ions and their effect on the photoluminescence properties of the BTB:xEu3+ phosphors are discussed in detail. The BTB:xEu3+,Na+ system demonstrated a strong thermal stability (68.4% at 150 °C), low color temperature (about 1940-1950 K) and high color purity (almost 90%). Furthermore, the prototype LED device can emit a bright white light, has a stable luminous efficiency and color rendering index, and the color gamut reaches 115.5% of the NTSC standard. Therefore, the BTB:xEu3+,Na+ series phosphors provide a better choice for the development of lighting and display devices with a wide color gamut.

Stable Tunable Luminescence of Hetero-valent Eu Ion Activated Ba2InTaO6 Phosphors Synthesized by Defect-Induced Self-Reduction in the Molten-Salt Method.

Functional materials with stable and adjustable luminescence have recently become a research hotspot for their broad application prospects. Tunable luminescence can be realized by the doping of hetero-valent europium ions. High-temperature hydrogen atmosphere reduction is required in the traditional preparation of Eu2+-doped phosphors. Herein, an anoxic molten-salt medium environment was established to form oxygen vacancy defects in the reaction system and induce the self-reduction of Eu3+ ions to obtain Eu2+ ions. X-ray photoelectron spectroscopy (XPS) results confirm the existence of Eu2+ and Eu3+ ions in the samples, and the fluorescence spectrum shows that hetero-valent Eu ions can synergistically emit light effectively. Under 266 nm ultraviolet light excitation, the white light emission was successfully realized for a Ba2InTaO6:Eu phosphor by different emission combinations of Eu3+ and Eu2+ ions. In addition, the Ba2InTaO6:Eu phosphor exhibits adjustable luminescence from greenish-yellow to red exciting at 390-490 nm, which has superior stability in a high-temperature and high-humidity environment. Therefore, it is very promising that Ba2InTaO6:Eu will be used as multi-color functional materials in many fields such as communication encryption and colorful decoration.

Decipher the Helicobacter pylori Protein Targeting in the Nucleus of Host Cell and their Implications in Gallbladder Cancer: An insilico approach.

Gallbladder cancer (GBC) is one of the leading causes of cancer-related mortality worldwide. Researchers have investigated that specific strains of bacteria are connected with growth of different types of cancers in human. Some reports show possible implication of Helicobacter pylori (H. pylori) in the etiology of gallbladder cancer (GBC). Their enigmatic mechanisms, nevertheless, are not still well clear. We sought to predict whether various proteins of H. pylori targeted to nucleus of host cells and their implication in growth of gallbladder cancer. GBC is one of the leading causes of cancer mortality worldwide. We applied bioinformatics approach to analyze the H. pylori proteins targeting into the nucleus of host cells using different bioinformatics predictors including nuclear localization signal (NLS) mapper Balanced Subcellular Localization (BaCelLo) and Hum-mPLoc 2.0. Various nuclear targeting proteins may have a potential role in GBC etiology during intracellular infection. We identified 46 H. pylori proteins targeted into nucleus of host cell through bioinformatics tools. These H. pylori nucleus-targeting proteins might alter the normal function of host cells by disturbing the different pathways including replication, transcription, translation etc. Various nucleus-targeted proteins can affect the normal growth and development of infected cells. We propose that H. pylori proteins targeting into the nucleus of host cells regulate GBC growth using different strategies. These integrative bioinformatics research demonstrated several H. pylori proteins that may serve as possible targets or biomarkers for early cure and treatment or diagnosis GBC.

Crystallographic Visualization of a Guest-Induced Solar-Driven Cycloaddition Reaction Based on a Recyclable Nonporous Coordination Polymer.

Stimuli-responsive solids with adjustable photophysical properties are particularly attractive because they can be used as smart materials in anticounterfeiting, information storage, holographic imaging, and other fields. Herein, we report a unique nonporous coordination polymer, {[Ag(3,3'-dpe)](2,2'-Hbpdc)}n (1; 3,3'-dpe = 1,2-dipyridin-3-ylethene and 2,2'-H2bpdc = 2,2'-biphenyldicarboxylic acid), that can convert to an extremely photoreactive compound, 1·H2O·MeCN (MeCN = acetonitrile), through guest capture. Upon irradiation of sunlight, 1·H2O·MeCN can transform to {[Ag(3,3'-tpcb)0.5](2,2'-Hbpdc)(H2O)(MeCN)}n (2·H2O·MeCN; 3,3'-tpcb = 1,2,3,4-tetrapyridin-3-ylcyclobutane). 2·H2O·MeCN can lose its solvent molecules to form 2 and further return to 1 at high temperature. Accompanied by direct visualization based on multistep single-crystal-to-single-crystal conversions, the recyclable crystalline solid exhibits remarkable fluorescence changes, which makes it a supramolecular switch for application in multiple anticounterfeiting.

Risk of cervical lesions in high-risk HPV positive women with normal cytology: a retrospective single-center study in China.

BACKGROUND: To investigate high-risk HPV (hr-HPV) genotype distributions and the association between hr-HPV infection with severity of the cervical lesions in women with normal cytology. METHODS: In this cross-sectional study, the result of the hr-HPV test and biopsy of colposcopy of women with normal cytology from January 2012 to January 2019 were analyzed. The detection rate of high-grade squamous intraepithelial lesion (HSIL) and cervical cancer were calculated among different hr-HPV genotypes, viral load group, and age groups. RESULTS: Five thousand eight hundred eighty women were enrolled in this study. Overall, 59.97% had normal histological results, 19.32% had HSIL, and 1.07% had cervical cancer. The detection rate of HSIL or worse (HSIL+) in women with single HPV16(34.00%), HPV31(27.50%), HPV33(25.58%), and HPV52(20.88%) infection were higher significantly than single HPV18 (15.59%) infection, respectively. The HSIL+ detection rate between HPV16 single infection and multiple infections (excluding HPV18) was no significant difference (34% vs 35.47%, P = 0.638), contrary to HPV18(12.59% vs 21.67%, P = 0.022). In women without HPV16/18 infections, HSIL+ detection rates for single, double, and triple or more hr-HPV infections were 12.28, 20.31, and 37.50%, the risk of detection of HSIL+ significantly increasing. With the hr-HPV DNA load increases, the risk of detection of HSIL+ (χ2 = 91.01, P < 0.0001) and invasive cervical cancer (χ2 = 5.757, P = 0.016) increase. In age < 30, 31-40, 41-50, 51-60, > 60 group, HSIL+ detection rate were 24.80%、22.10%、19.59%、14.29, and 12.61%, respectively. CONCLUSION: Women who have normal cytology with HPV 16/18/31/33/52/58 infections, multiple HPV infections and high viral load, have a higher detection rate of HSIL+.

LINC01006 promotes cell proliferation and metastasis in pancreatic cancer via miR-2682-5p/HOXB8 axis.

BACKGROUND: Pancreatic cancer (PC) is one of the deadliest cancers about the digestive system. Recent researches have validated that long non-coding RNAs (lncRNAs) play vital roles in various cancers, while the function of LINC01006 in PC is rarely clarified. AIM OF THE STUDY: Investigation of the specific role of LINC01006 in PC. METHODS: LINC01006 expression was examined by RT-qPCR. CCK-8, EdU, transwell, wound healing, and western blot assays were carried out to explore the function of LINC01006 in PC. The interaction among LINC01006, miR-2682-5p and HOXB8 was verified by luciferase reporter, RIP and ChIP assays. RESULTS: The expression of LINC01006 was markedly upregulated in PC tissues and cells. Furthermore, LINC01006 knockdown inhibited PC cell proliferation, invasion and migration, and upregulation of LINC01006 led to the opposite results. Besides, miR-2682-5p expression was downregulated and negatively regulated by LINC01006 in PC. Meanwhile, LINC01006 could bind with miR-2682-5p in PC. Moreover, miR-2682-5p negatively regulated HOXB8 expression and there was a binding site between miR-2682-5p and HOXB8 in PC. Additionally, miR-2682-5p overexpression or HOXB8 knockdown rescued the promotive effects of LINC01006 upregulation on PC cell progression. Similarly, miR-2682-5p inhibition or HOXB8 overexpression countervailed the repressive role of LINC01006 downregulation in PC cell progression. In addition, the transcription factor HOXB8 could activate LINC01006 transcription in PC. CONCLUSIONS: LINC01006 promotes cell proliferation and metastasis in pancreatic cancer via miR-2682-5p/HOXB8 axis, which may facilitate the treatment for PC.

RASSF7 promotes cell proliferation through activating MEK1/2-ERK1/2 signaling pathway in hepatocellular carcinoma.

The Ras-association domain family (RASSF) proteins have been involved in many important biological processes. RASSF7 is recently reported to be up-regulated in several types of cancer. However, the function of RASSF7 remain unknown in human cancers. To explore the role of RASSF7 in hepatocellular carcinoma (HCC) cells proliferation and molecular mechanism. RASSF7 expression was examined using public database TCGA, qRT-PCR and Western blot. The correlation between RASSF7 and clinicopathological features was measured. Overexpression and silencing of RASSF7 were performed to measure the impact on HCC cell proliferation, cell cycle and apoptosis. Futhermore, the molecular mechanism of MEK1/2-ERK1/2 signaling pathway regulation by RASSF7 was explored. RASSF7 was significantly up-regulated in HCC tissues and cell lines, and correlated with AFP, poor tumor histology and T stage. Overexpression of RASSF7 promoted HCC cell proliferation, drived G1-S phase cell cycle transition and inhibited apoptosis. Knockdown of RASSF7 suppressed cell growth, induced G1-S phase cell cycle arrest and cell apoptosis. Furthermore, our findings also demonstrated that RASSF7 promoted HCC cell proliferation through activating MEK1/2-ERK1/2 signaling pathway. Taken together, this study provides a novel evidence for clinical significance of RASSF7 as a potential biomarker, and demonstrates that RASSF7- MEK1/2-ERK1/2 signaling pathway might be a novel pathway involved in HCC progression.

Unexpected formation of scheelite-structured Ca1-xCdxWO4 (0 ≤ x ≤ 1) continuous solid solutions with tunable photoluminescent and electronic properties.

Design of a solid solution with tunable functionality is an attractive strategy toward realizing novel devices with multi-functionalities. In this work, a series of Ca1-xCdxWO4 solid solutions in the entire range 0 ≤ x ≤ 1 with tetragonal scheelite structure have been successfully prepared for the first time. X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectroscopies indicated that all the nanocrystals have a tetragonal scheelite structure without wolframite phase. Structural refinement data revealed that the lattice volume decreased with the replacement of Ca2+ by Cd2+ ions. UV-Vis diffuse reflectance spectra indicated that optical band gap reduced with the replacement of Ca2+ by Cd2+ ions. Scanning electron microscopic (SEM) images showed that morphologies of the nanocrystals changed with the chemical compositions. The structure evolution of the solid solutions was further investigated by high-resolution transmission electron microscopy (HRTEM). Moreover, the influence of chemical compositions on the photoluminescent and electric performance has been performed and discussed. The reported synthetic approach and findings reported here are important to understand the structure and structure-property relation of scheelite-structured tungstate and molybdate compounds, which has potential applications in the design of other kinds of novel functional materials.

[Stem cell factor enhances invasive ability of BxPC-3 cells via hypoxia-inducible factor 1α (HIF-1α)].

Objective To investigate the effect of stem cell factor (SCF)/c-KIT system on the invasion of BxPC-3 pancreatic cancer cells and the role of hypoxia-inducible factor 1 alpha (HIF-1α) in this effect. Methods BxPC-3 cells were cultured in normoxia and hypoxia. The cells cultured in normoxia were treated with SCF. Real-time quantitative PCR and Western blotting were used to investigate the expressions of HIF-1α mRNA and protein, respectively. Small interference RNA of HIF-1α (siHIF-1α) was designed and synthesized, and then transfected into BxPC-3 cells. The expressions of matrix metalloproteinase-2 (MMP2), MMP9, and urokinase type plasminogen activator (uPA) were detected by real-time quantitative PCR and Western blotting in BxPC-3 cells after treated with SCF or siHIF-1α. The effects of SCF/c-KIT and HIF-1α knockdown on BxPC-3 cell invasion were examined by TranswellTM assay. Results Either SCF or hypoxia could induce the protein expression of HIF-1α. The siHIF-1α down-regulated the expression of HIF-1α specifically in BxPC-3 cells. SCF up-regulated the mRNA and protein expressions of MMP2, MMP9 and uPA, while siHIF-1α down-regulated the expressions of these genes. The invasive ability of BxPC-3 cells were enhanced by SCF, while siHIF-1α played an opposite role. Conclusion SCF/c-KIT system up-regulates the mRNA and protein expressions of MMP2, MMP9 and uPA through HIF-1α, which enhances the invasive ability of pancreatic cancer cells. And siHIF-1α can effectively inhibit these effects.

[Expressions of stem cell factor and hypoxia inducible factor 1 alpha in pancreatic cancer cells and related mechanism].

Objective To study the correlation between the expressions of stem cell factor (SCF) and hypoxia inducible factor 1 alpha (HIF-1α) in pancreatic cancer, and investigate the mechanism by which SCF regulates the expression of HIF-1α. Methods Immunohistochemistry was used to detect the expressions of SCF and HIF-1α in pancreatic cancer specimens and to analyze the correlation between SCF and HIF-1α expressions. Pancreatic cancer PANC-1 cells were treated with different doses of SCF (0, 1, 10, 100 ng/mL) alone or combined with c-KIT inhibitor Gleevec (5 µmol/L). Real-time fluorescent quantitative PCR (qRT-PCR) was performed to detect the level of HIF-1α mRNA, and Western blotting to detect the HIF-1α protein level, the phosphorylation levels of ERK1/2 and AKT. Results SCF and HIF-1α were up-regulated in pancreatic cancer samples and they had an obvious positive correlation. In PANC-1 cells, SCF didn't affect the expression of HIF-1α mRNA, but up-regulated the expression of HIF-1α protein in a dose-dependent manner. Gleevec inhibited the SCF-induced up-regulation of HIF-1α protein, but did not affect the mRNA. And Gleevec blocked the phosphorylation of AKT and ERK1/2. Conclusion SCF/c-KIT can up-regulate the protein expression of HIF-1α by activating AKT and ERK signaling pathways in pancreatic cancer cells.