The Multifunction of TRIM26: From Immune Regulation to Oncology.

Ubiquitination, a crucial post-translational modification, plays a role in nearly all physiological processes. Its functional execution depends on a series of catalytic reactions involving numerous proteases. TRIM26, a protein belonging to the TRIM family, exhibits E3 ubiquitin ligase activity because of its RING structural domain, and is present in diverse cell lineages. Over the last few decades, TRIM26 has been documented to engage in numerous physiological and pathological processes as a controller, demonstrating a diverse array of biological roles. Despite the growing research interest in TRIM26, there has been limited attention given to examining the protein's structure and function in existing reviews. This review begins with a concise overview of the composition and positioning of TRIM26 and then proceeds to examine its roles in immune response, viral invasion, and inflammatory processes. Simultaneously, we demonstrate the contribution of TRIM26 to the progression of various diseases, encompassing numerous malignancies and neurologic conditions. Finally, we have investigated the potential areas for future research on TRIM26.

Survey of Heterodera glycines population abundance and virulence phenotypes during 2021-2022 in Heilongjiang Province.

Soybean cyst nematode (SCN), Heterodera glycines, poses a significant threat to global soybean production. Heilongjiang, the largest soybean-producing province in China, contributes over 40% to the country's total yield. This province has much longer history of SCN infestation. To assess the current situation in Heilongjiang, we conducted a survey to determine the SCN population density and virulence phenotypes during 2021-2022 and compared the data with a previous study in 2015. A total of 377 soil samples from 48 counties representing eleven major soybean-planting regions were collected. The prevalence of SCN increased from 55.4% in 2015 to 59% in the current survey. The population densities ranged from 80 to 26,700 eggs and juveniles per 100 cm3 of soil. Virulence phenotypes were evaluated for 60 representative SCN populations using the HG type test, revealing nine different HG types. The most common virulence phenotypes were HG types 7 and 0, accounting for 56.7% and 20% of all SCN populations, respectively. The prevalence of populations with a reproductive index (FI) greater than 10% on PI548316 increased from 64.5% in 2015 to 71.7%. However, the FI on the commonly used resistance sources PI 548402 (Peking) and PI 437654 remained low at 3.3%. These findings highlight the increasing prevalence and changing virulence phenotypes of SCN in Heilongjiang. They also emphasize the importance of rotating soybean varieties with different resistance sources and urgently identifying new sources of resistance to combat SCN.

Gastric Submucosal Fat Accumulation Is Associated with Insulin Resistance in Patients with Obesity.

PURPOSE: Ectopic fat accumulation plays a significant role in obesity-related metabolic dysfunction, and few studies have reported an association between ectopic gastric fat and metabolic risk factors. We aim to fulfill this need by assessing the degree of gastric submucosal fat accumulation in pathologic sections of 190 sleeve gastrectomy specimens. METHODS: Study patients were divided into two groups (D1 and D2) based on whether fat accumulation exceeded 1/3 of the submucosa of the stomach. Demographic and metabolic risk factors were compared between the two groups. Metabolic risk variables that might be associated with the degree of fat accumulation were screened in the original cohort. After balancing for possible confounders, the robustness of the correlations was assessed using binary and conditional logistic regression analyses. RESULTS: All study patients had fat accumulation in the submucosa of the stomach. C-reactive protein (CRP), body mass index (BMI), visceral fat area (VFA), and insulin resistance (IR) were higher in the D2 group than in the D1 group in the original cohort (P < 0.05). Logistic regression analysis showed that BMI and IR may be associated with increased fat accumulation. After balancing variables other than obesity indicators and IR using propensity score matching, BMI and IR remained significantly different between the two groups (P < 0.05). Further analysis of the matched cohort using two logistic regression analyses showed that IR was an independent risk factor for increased fat accumulation. CONCLUSION: This study indicated that gastric submucosal fat accumulation was prevalent in patients with obesity and was associated with IR.

Deep learning-derived spatial organization features on histology images predicts prognosis in colorectal liver metastasis patients after hepatectomy.

Histopathological images of colorectal liver metastases (CRLM) contain rich morphometric information that may predict patients' outcomes. However, to our knowledge, no study has reported any practical deep learning framework based on the histology images of CRLM, and their direct association with prognosis remains largely unknown. In this study, we developed a deep learning-based framework for fully automated tissue classification and quantification of clinically relevant spatial organization features (SOFs) in H&E-stained images of CRLM. The SOFs based risk-scoring system demonstrated a strong and robust prognostic value that is independent of the current clinical risk score (CRS) system in independent clinical cohorts. Our framework enables fully automated tissue classification of H&E images of CRLM, which could significantly reduce assessment subjectivity and the workload of pathologists. The risk-scoring system provides a time- and cost-efficient tool to assist clinical decision-making for patients with CRLM, which could potentially be implemented in clinical practice.

Fully physical crosslinked BSA-based conductive hydrogels with high strength and fast self-recovery for human motion and wireless electrocardiogram sensing.

The emergence of protein hydrogel sensors has attracted intensive attention because of their biocompatibility and biodegradability, and potential application in wearable electronics. However, natural protein hydrogel sensors commonly exhibited low conductivity, weak mechanical strength, and unsatisfactory self-recovery performance. Herein, a fully physical crosslinked conductive BSA-MA-PPy/P(AM-co-AA)/Fe3+ hydrogel based on methacrylic anhydride (MA)-modified and polypyrrole (PPy)-functionalized bovine serum albumin (BSA) introduced into poly(acrylamide-co-acrylic acid) (P(AM-co-AA)) matrix was constructed. Due to the presence of the hydrogen bond complexation and the metal-ligand coordination between ferric ion (Fe3+) and the polymer chain, the as-prepared hydrogel showed outstanding mechanical strength (5.36 MPa tensile stress, 17.66 MJ/m3 toughness, and 1.61 MPa elastic modulus) and fast self-recovery performance (99.89 %/96.18 %/93.57 % stress/elastic modulus/dissipated energy within 10 min at room temperature). Meanwhile, the hydrogel exhibited outstanding conductivity (1.13 S/m) due to the presence of PPy and Fe3+ moieties, high strain sensitivity (GF = 4.98) and good biocompatibility without causing skin allergic reactions. Thus, the hydrogel can be fabricated into strain sensor to monitor the joint motion of the human body. Moreover, it can be used as soft electrode in electrocardiogram device to realize wireless heart-rate monitoring in the real-time conditions (relaxation and post-exercising), which exhibited excellent reusability, stability, and reliability simultaneously.

NOL6 Regulates the Proliferation and Apoptosis of Gastric Cancer Cells via Regulating TP53I3, CDK4 and MCM7 Expression.

Background: Gastric cancer (GC) is a prevalent cancer with high mortality and strong invasiveness, and the entire regulatory networks of GC is still unclear. Objective: The aim of this study was to explore the specific mechanism of the effect of nucleolar protein 6 (NOL6) on the proliferation and apoptosis of GC cells. Methods: The human gastric adenocarcinoma cell line HGC-27 and AGS were cultured. qRT-PCR was used to verify the expression level of NOL6 in GC cells; MTT and EdU were used to test cell proliferation; TUNEL staining and Flow cytometry were used to detect cell apoptosis; The downstream genes and pathways following NOL6 knockdown were explored through the microarray assay and ingenuity pathway analysis, and the downstream genes were finally verified by qRT-PCR and Western blotting. The xenograft mice were used to investigate the effect of NOL6 on GC in vivo. Results: TCGA data analysis showed that NOL6 expression level was higher in GC cells than adjacent normal cells. Over-expression of NOL6 increased proliferation and colony formation, and inhibited the apoptotic rate in AGS and HGC-27 cells, while NOL6 knockdown induced the opposite effects. Through microarray assay and IPA analysis, NOL6-related downstream genes and critical signaling pathways were found. And we verified the relationship between downstream genes and GC. Additionally, NOL6 knockdown could decrease the weight and volume of tumor in the mice. Conclusion: NOL6 knockdown could inhibit cell proliferation and induce cell apoptosis of GC, suggesting that NOL6 may serve as a potential therapeutic target for treating GC.

Ultrasensitive, label-free voltammetric determination of norfloxacin based on molecularly imprinted polymers and Au nanoparticle-functionalized black phosphorus nanosheet nanocomposite.

Norfloxacin (NOR) is an antibiotic commonly used to treat humans and food-producing animals. Owing to NOR abuse, its residues are frequently found in animal-derived food products and the surrounding environment. Therefore, development of an efficient analytical technique for the selective determination of trace NOR is greatly significant for food safety and environmental protection. Here, we fabricated an ultrasensitive, label-free molecularly imprinted polymer (MIP) voltammetric sensor for the selective determination of NOR, based on an Au nanoparticle-functionalized black phosphorus nanosheet nanocomposite (BPNS-AuNP) covered by a polypyrrole-imprinted film. BPNS-AuNP nanocomposites were prepared via an in-situ one-step method without the use of reducing agents. The imprinted polypyrrole film was formed on the surface of the BPNS-AuNPs in the presence of NOR. The physical properties and electrochemical behavior of the MIP/BPNS-AuNPs were investigated using various characterization techniques, and the analytical parameters were optimized. We found that BPNS-AuNPs improve the ambient stability and electrocatalytic activity, providing a large surface area for locating a higher number of specific recognition sites. Consequently, the MIP/BPNS-AuNP/GCE showed excellent sensing performance toward NOR, with a wide linear response range (0.1 nM - 10 µM), an extremely low limit of detection (0.012 nM), and extraordinary selectivity. Moreover, the MIP/BPNS-AuNP/GCE was used to determine NOR in various experimental samples with satisfactory results.

l-Cysteine-Modified Graphene Oxide-Based Membrane for Chiral Selective Separation.

A novel chiral separation membrane was fabricated by assembling l-cysteine (l-Cys)-modified graphene oxide sheets. l-Cys modification leads to an enantiomer separation membrane with an accessible interlayer spacing of 8 Å, which allows high solvent permeability. In the racemate separation experiments under isobaric conditions, the enantiomeric excess (ee) values of alanine (Ala), threonine (Thr), tyrosine (Tyr), and penicillamine (Pen) racemates in the permeation solution were 43.60, 44.11, 27.43, and 46.44%, respectively. In the racemate separation experiments under negative pressure, the separation performances of Ala, Thr, and Tyr were still maintained, and the enantiomeric excess (ee) values of the filtrate after separation were 56.80, 54.57, and 32.34%, respectively. These results indicate that the as-prepared GO-Cys membrane has a great practical value in the field of enantiomer separation.

Molecular Dynamics Simulations of Cholesterol Effects on the Interaction of hIAPP with Lipid Bilayer.

Fundamental understanding of specific interactions of human islet amyloid polypeptide (hIAPP) with cell membrane is critical for elucidating the underlying pathogenesis of type II diabetes mellitus (T2DM). Membrane cholesterol is known to regulate membrane functions and properties, but its exact role in driving hIAPP-membrane interactions still remains controversial. In this work, we computationally investigated the concentration effect of cholesterol on the adsorption, orientation, and surface interaction of hIAPP oligomers on POPC bilayers containing different amounts of cholesterol (χ = 0, 20, and 40 mol %). Collective MD simulations consistently showed that an increased cholesterol level modulated the structure and dynamics of POPC bilayer, leading to an increase of bilayer thickness, lipid packing order, and surface hydrophobicity but a decrease of lipid mobility. Cholesterol-induced bilayer changes further caused hIAPP oligomer to more preferentially bind to POPC bilayer in the presence of cholesterol via C-terminal residues, in contrast to weak or no binding of hIAPP oligomer on pure POPC bilayers. The cholesterol-enhanced hIAPP-membrane binding is mainly contributed by electrostatic interactions between C-terminal residues and lipid head groups, which may explain the rapid adsorption and aggregation of hIAPP in the presence of cholesterol in cell membranes. This computational work provides some insights into drug development and therapeutic strategies for T2DM by considering cholesterol effects.

A versatile luminescent resonance energy transfer (LRET)-based ratiometric upconversion nanoprobe for intracellular miRNA biosensing.

Rational design and fabrication of bio-nanoprobes for intracellular miRNA biosensing are highly desired for early clinical diagnosis and prognosis. Herein, we have developed a versatile LRET-based ratiometric (LBRU) nanoprobe of NaYF4:Yb,Er@NaYF4@NH2-mSiO2/rhodamine B/C-DNA sandwich-structured nanocomposites for intracellular miRNA biosensing. The nanoprobe was composed of NaYF4:Yb,Er@NaYF4 upconversion nanoparticles (energy donor) with an amino functionalized mesoporous silica shell (NH2-mSiO2), rhodamine B (acceptor) loaded into the mesopores of NH2-mSiO2, and the complementary sequences of target miRNA (denoted as C-DNA) acting as recognition species wrapped on the nanocomposite. Due to the LRET behavior between donors and acceptors, the loaded rhodamine B can quench the green upconversion emission of NaYF4:Yb,Er@NaYF4 at 540 nm completely. Moreover, it can be released from the nanocomposite in the presence of target miRNA, which blocked the LRET behavior to "turn on" the green upconversion luminescence. Besides, as the unaffected red upconversion luminescence (at 660 nm) can be used as an internal standard to provide built-in correction for environmental effects, the intensity ratio of upconversion luminescence at 540 and 660 nm (I540/I660) was employed as the output signal to afford an accurate detection of target miRNA. Due to the biocompatibility, high photostability and low auto-fluorescence background, the nanoprobe was successfully utilized to diagnose the intracellular miRNA-21 expression in MCF-7 cells via upconversion fluorescence imaging. We envision that the proposed LBRU nanoprobe has great potential applications in early cancer diagnosis.

Lost miR-141 and upregulated TM4SF1 expressions associate with poor prognosis of pancreatic cancer: regulation of EMT and angiogenesis by miR-141 and TM4SF1 via AKT.

Background: Transmembrane-4-L-six-family-1 (TM4SF1) functions to regulate cell growth and mobility and TM4SF1 expression was upregulated in pancreatic cancer. This study further investigated the role of TM4SF1 in regulating pancreatic cancer epithelial-mesenchymal transition (EMT) and angiogenesis and the underlying molecular events.Methods: Tissue specimens were collected from 90 pancreatic cancer patients for immunohistochemical and qRT-PCR analysis of miR-141 and TM4SF1 levels, respectively. Pancreatic cancer cell lines were used for in vitro assays, while nude mice were used for the in vivo assay.Results: TM4SF1 expression was upregulated, whereas miR-141 expression was lost in pancreatic cancer tissues, both of which was associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Furthermore, miR-141 was able to target and reduce TM4SF1 expression in pancreatic cancer cells and miR-141 expression inhibited pancreatic cancer cell EMT in vitro and Matrigel plug angiogenesis and lung metastasis in nude mice. At the gene level, miR-141 directly targeted and reduced TM4SF1 expression and in turn induced E-cadherin expression and reduced VEGF-A expression by suppressing activation of the AKT signaling pathway.Conclusions: This study demonstrated that upregulated TM4SF1 and lost miR-141 expression were associated with advanced clinicopathological features and poor survival of pancreatic cancer patients. Lost miR-141 expression but induced TM4SF1 expression altered expression of VEGF-A and E-cadherin and promoted pancreatic cancer cell EMT and angiogenesis via the AKT signaling pathway, suggesting that targeting of miR-141 and TM4SF1 may be a potential therapeutic strategy to control pancreatic cancer.

Key genes associated with pancreatic cancer and their association with outcomes: A bioinformatics analysis.

Pancreatic cancer is a highly malignant neoplastic disease of the digestive system. In the present study, the dataset GSE62165 was downloaded from the Gene Expression Omnibus (GEO) database. GSE62165 contained the data of 118 pancreatic ductal adenocarcinoma samples (38 early­stage tumors, 62 lymph node metastases and 18 advanced tumors) and 13 control samples. Differences in the expression levels of genes between normal tissues and early­stage tumors were investigated. A total of 240 differentially expressed genes (DEGs) were identified using R software 3.5 (137 upregulated genes and 103 downregulated genes). Then, the differentially expressed genes were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. The following 18 core genes were identified using Cytoscape, based on the protein­interaction network of DEGs determined using the online tool STRING: EGF, ALB, COL17A1, FN1, TIMP1, PLAU, PLA2G1B, IGFBP3, PLAUR, VCAN, COL1A1, PNLIP, CTRL, PRSS3, COMP, CPB1, ITGA2 and CEL. The pathways of the core genes were primarily associated with pancreatic secretion, protein digestion and absorption, and focal adhesion. Finally, survival analyses of core genes in pancreatic cancer were conducted using the UALCAN online database. It was revealed that PLAU and COL17A1 were significantly associated with poor prognosis (P<0.05). The expression levels of genes in primary pancreatic cancer tissues were then compared; only one gene, COL17A1, was identified to be significantly differentially expressed. Finally, another dataset from GEO, GSE28735, was analyzed to verify the upregulated expression of COL17A1. Taken together, the results of the present study have indicated that the expression of COL17A1 gene may be associated with the occurrence and development of pancreatic cancer.

Biosynthesis of pneumocandin lipopeptides and perspectives for its production and related echinocandins.

Fungal diseases are a global public health problem. Invasive fungal infections pose a serious threat to patients with compromised immune systems, such as those undergoing organ or bone marrow transplants, cancer, or HIV/AIDS. Pneumocandins are antifungal lipohexapeptides of the echinocandin family that noncompetitively inhibit of 1,3-ß-glucan synthase of fungal cell wall and provide the precursor for the semisynthesis of caspofungin, which is widely used as first-line therapy for invasive fungal infections. Recently, the biosynthetic steps leading to formation of pneumocandin B0 and echinocandin B have been elucidated, and thus, provide a framework and attractive model for further design new antifungal therapeutics around natural variations in echinocandin structural diversities via genetic and chemical tools. In this article, we analyze the biosynthetic pathway of pneumocandins and other echinocandins, provide an update on the array of pneumocandin analogues generated by genetic manipulation, and summarize advances in the enhancement of pneumocandin B0 production by random mutagenesis and fermentation optimization. We also give offer advice on the development of improved pneumocandin drug candidates and more efficient production of pneumocandin B0.

Experimental and Computational Protocols for Studies of Cross-Seeding Amyloid Assemblies.

Alzheimer's disease (AD) and type 2 diabetes (T2D) are two common protein aggregation diseases. Compelling evidence has shown a link between AD and T2D, which may derive from interspecies cross-sequence interactions between amyloid-ß peptide (Aß), associated with AD, and human islet amyloid polypeptide (hIAPP), associated with T2D. Herein, we present experimental and computational protocols and tools to study the aggregate structures and kinetics, conformational conversion, and molecular interactions of Aß-hIAPP mixtures. These protocols could be generally applied to other cross-seeding behaviors of amyloid peptides.

Genistein: A Dual Inhibitor of Both Amyloid ß and Human Islet Amylin Peptides.

Abnormal misfolding and aggregation of amyloid peptides into amyloid fibrils are common and critical pathological events in many neurodegenerative diseases. Most inhibitors or drugs have been developed to prevent amyloid aggregation of a specific peptide, showing sequence-dependent inhibition mechanisms. It is more challenging to develop or discover inhibitors capable of preventing the aggregation of two or more different amyloid peptides. Genistein, a major phytoestrogen in soybean, has been widely used as an anti-inflammation and cerebrovascular drug due to its antioxidation and antiacetylcholinesterase effects. Herein, we examine the inhibitory effects of genistein on the aggregation of amyloid-ß (Aß, associated with Alzheimer's disease) and human islet amylin (hIAPP, associated with type 2 diabetes) and Aß- and hIAPP-induced neurotoxicity using a combination of experimental and computational approaches. Collective experimental results from thioflavin T (ThT), atomic force microscopy (AFM), and circular dichroism (CD) demonstrate that genistein shows strong inhibition ability to prevent the conformational transition of both Aß and hIAPP monomers to ß-sheet structures, thus reducing final amyloid fibrillization from Aß and hIAPP monomer aggregation by 40-63%. Further 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and large unilamellar vesicle (LUV) assays show that genistein helps to increase cell viability, decrease cell apoptosis, and reduce cell membrane leakage, where the cell protection effect of genistein is likely correlated with its reduced membrane leakage. Comparative molecular dynamics (MD) simulations reveal that genistein prefers to bind the ß-sheet groove, a common structural motif of amyloid fibrils, of both Aß and hIAPP oligomers to interfere with their self-aggregation. This work for the first time demonstrates genistein as a dual inhibitor of Aß and hIAPP aggregation. Further structural optimization and refinement of genistein may generate a series of effective sequence-independent inhibitors against the aggregation and toxicity of different amyloid peptides.

Membrane Interactions of hIAPP Monomer and Oligomer with Lipid Membranes by Molecular Dynamics Simulations.

Interaction of human islet amyloid polypeptide (hIAPP) peptides with cell membrane is crucial for the understanding of amyloid toxicity associated with Type II diabetes (T2D). While it is known that the hIAPP-membrane interactions are considered to promote hIAPP aggregation into fibrils and induce membrane disruption, the membrane-induced conformation, orientation, aggregation, and adsorption behaviors of hIAPP peptides have not been well understood at the atomic level. Herein, we perform all-atom explicit-water molecular dynamics (MD) simulations to study the adsorption, orientation, and surface interaction of hIAPP aggregates with different sizes (monomer to tetramer) and conformations (monomer with α-helix and tetramer with ß-sheet-rich U-turn) upon adsorption on the lipid bilayers composed of both pure zwitterionic POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and mixed anionic POPC/POPE (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) (3:1) lipids. MD simulation results show that hIAPP monomer with α-helical conformation and hIAPP pentamer with ß-sheet conformation can adsorb on both POPC and POPC/POPE bilayers via a preferential orientation of N-terminal residues facing toward the bilayer surface. The hIAPP aggregates show stronger interactions with mixed POPC/POPE lipids than pure POPC lipids, consistent with experimental observation that hIAPP adsorption and fibrililation are enhanced on mixed lipid bilayers. While electrostatic interactions are main attractive forces to drive the hIAPP aggregates to adsorb on both bilayers, the introduction of the more hydrophilic head groups of POPE lipids further promote the formation of the interfacial hydrogen bonds. Complement to our previous studies of hIAPP aggregates in bulk solution, this computational work increases our knowledge about the mechanism of amyloid peptide-membrane interactions that is central to the understanding the progression of all amyloid diseases.

Long Noncoding RNA H19 in Digestive System Cancers: A Meta-Analysis of Its Association with Pathological Features.

Long noncoding RNA (lncRNA) H19 has been reported to be upregulated in malignant digestive tumors, but its clinical relevance is not yet established. The meta-analysis was to investigate the association between H19 expression and pathological features of digestive system cancers. The databases of PubMed, EMBase, Web of Science, CNKI, and WanFang were searched for the related studies. A total of 478 patients from 6 studies were finally included. The meta-analysis showed that the patient group of high H19 expression had a higher risk of poorly differentiated grade, deep tumor invasion (T2 stage or more), lymph node metastasis, and advanced TNM stage than the group of low H19 expression, although there was no difference between them in terms of distant metastasis. Therefore, the high expression of lncRNA H19 might predict poor oncological outcomes of patients with digestive system cancers.

A Novel Insecticidal Peptide SLP1 Produced by Streptomyces laindensis H008 against Lipaphis erysimi.

Aphids are major insect pests for crops, causing damage by direct feeding and transmission of plant diseases. This paper was completed to discover and characterize a novel insecticidal metabolite against aphids from soil actinobacteria. An insecticidal activity assay was used to screen 180 bacterial strains from soil samples against mustard aphid, Lipaphis erysimi. The bacterial strain H008 showed the strongest activity, and it was identified by the phylogenetic analysis of the 16S rRNA gene and physiological traits as a novel species of genus Streptomyces (named S. laindensis H008). With the bioassay-guided method, the insecticidal extract from S. laindensis H008 was subjected to chromatographic separations. Finally, a novel insecticidal peptide was purified from Streptomyces laindensis H008 against L. erysimi, and it was determined to be S-E-P-A-Q-I-V-I-V-D-G-V-D-Y-W by TOF-MS and amino acid analysis.

Association between the p73 gene G4C14-to-A4T14 single nucleotide polymorphism and risk of cervical cancer by high resolution melting and PCR with confronting two-pair primers in a Chinese population.

As a member of the p53 gene family, the p73 gene can affect an individual's susceptibility to cancer through a p53-like manner. DNA sequence variation in the p73 gene has been reported to be associated with cancer risk. The present study aimed to identify whether the p73 gene G4C14-to-A4T14 single nucleotide polymorphism (SNP) is associated with risk of cervical cancer in a Chinese population. The p73 G4C14-to-A4T14 polymorphism was genotyped in 175 cervical cancer and 189 healthy control peripheral blood DNA samples using high resolution melting, polymerase chain reaction with confronting two-pair primers and direct DNA sequencing. The results demonstrated that carriers of the AT/AT genotype were associated with a significantly increased risk of cervical cancer (P=0.042; χ2=4.122; odds ratio = 2.241; 95% confidence interval = 1.013-4.956) compared with the GC/GC genotype carriers. In addition, there was a significant association between p73 genotypes and tumor size in patients with cervical cancer (P=0.014; χ2=8.607). However, no association was identified between p73 genotypes and tumor stage, histological type or lymph node metastasis in patients with cervical cancer. These results suggest that the p73 G4C14-to-A4T14 SNP may function as a marker of genetic susceptibility to cervical cancer in the Chinese population.

Overexpression of serine/threonine-protein kinase-1 in pancreatic cancer tissue: Serine/threonine-protein kinase-1 knockdown increases the chemosensitivity of pancreatic cancer cells.

Serine/threonine-protein kinase-1 (SMG-1) belongs to the phosphatidylinositol 3­kinase­related kinase family. Altered expression of SMG-1 contributes to human carcinogenesis and cancer progression. The present study detected the expression levels of SMG-1 in normal and cancerous pancreatic tissues and then assessed the effects of SMG-1-knockdown in pancreatic cancer cell lines in vitro. A pancreatic cancer tissue array and pancreatic cancer cell lines were used to detect the expression levels of SMG-1 and a lentivirus expressing either SMG-1 or negative control short hairpin (sh)RNA were used to knock down the expression of SMG-1 in the pancreatic cancer cell lines. Western blot, cell proliferation, Cell Counting kit-8, Transwell tumor cell migration and invasion assays, and flow cytometric analysis of cell apoptosis with or without gemcitabine or cisplatin treatment were performed to assess the tumor cells. The protein expression of SMG-1 was higher in the pancreatic cancer tissues and cells compared with the normal tissues. sh-SMG-1 lentivirus infection significantly suppressed the expression of SMG-1 in the pancreatic cancer cell lines, resulting in the inhibition of tumor cell proliferation and increased chemosensitivity to treatment with gemcitabine and cisplatin. However, SMG-1 knockdown had no effect on pancreatic cancer cell migration or invasion capacities. The protein expression of SMG-1 was increased in the pancreatic cancer tissues and was associated with an advanced tumor stage. Knock down of the expression of SMG-1 inhibited tumor cell proliferation and induced the chemosensitivity of pancreatic cancer cells in vitro.