The development of magnetic particles for cell separation is a promising and actively developing direction. An important requirement for this method of isolation is the preservation of cell viability for the possibility of further study. The aim of the work was to develop magnetic composites based on iron oxide for single-stage cell separation and to evaluate the possibilities of further study of these cells using molecular and cellular biology methods. The particles were synthesized by the precipitation method; the magnetic cores were embedded in silica using TEOS and APTES reagents. Anti-EpCAM antibodies were immobilized on the surfaces of the obtained composites. T24 cells containing this antigen on the surface of some cells were used as a model suspension. It was shown that incubation of particles with the cells led to a decrease in the proportion of EpCAM-positive cells in the suspension and their binding to the magnetic composites. During the first hour of incubation with the particles, a decrease in the proportion of living cells in the suspension and a change in the mRNA level of the BCL2 gene were noted. However, after 2 h of incubation, cell adaptation and restoration of viability were noted. The separation procedure resulted in a stable decrease in the expression of the BIRC5 gene. The cells that were immobilized were subsequently successfully cultured. Thus, the proposed particles do not have high requirements for synthesis but allow for the isolation of living cells that can be used for further studies.

Neuroblastoma (NB) is an aggressive pediatric malignancy that accounts for nearly 15% of all childhood cancer-related deaths, with high-risk cases showing a poor 20% prognosis and limited response to current therapies. Survivin, encoded by the BIRC5 gene, is an anti-apoptotic protein frequently overexpressed in NB and linked to treatment resistance and unfavorable clinical outcomes. An analysis of 1235 NB patient datasets revealed a significant association between elevated BIRC5 expression and reduced overall and event-free survival, highlighting survivin as an important therapeutic target in NB. To explore this strategy, we evaluated the efficacy of YM-155, a small-molecule survivin inhibitor, across multiple NB cell lines. YM-155 displayed potent cytotoxic activity in six NB cell lines with IC50 values ranging from 8 to 212 nM and significantly inhibited colony formation and 3D spheroid growth in a dose-dependent manner. Mechanistic analyses revealed that YM-155 downregulated survivin at both mRNA and protein levels, induced apoptosis by about 2-7-fold, and caused G0/G1 phase cell cycle arrest. Moreover, YM-155 treatment enhanced p53 expression, suggesting reactivation of tumor suppressor pathways. Notably, combining YM-155 and the chemotherapeutic agent etoposide resulted in synergistic inhibition of NB growth with ED75 values ranging from 0.17 to 1, compared to either agent alone. In the xenograft mouse model, YM-155 inhibited tumor burden in contrast to controls by about 3-fold, and without any notable toxic effects in vivo. Overall, our findings identify YM-155 as a promising therapeutic agent for high-risk NB by directly targeting survivin and enhancing chemosensitivity. These results support continued preclinical development of survivin inhibitors as part of rational combination strategies in pediatric cancer treatment.

Gill function in gas exchange and ion regulation is crucial for ionoregulatory homeostasis in teleost fishes, yet further research is needed to elucidate how cold stress affects these processes, particularly in relation to salinity-dependent tolerability. Indian medaka (Oryzias melastigma) were acclimated to freshwater (FW) and seawater (SW) environments before being exposed to cold stress at 18 °C for 168h. The protein abundance of the apoptotic marker Caspase-3 increased significantly in SW-acclimated fish compared to controls, indicating a heightened apoptotic response under cold stress in SW conditions. Concurrently, the expression of the anti-apoptotic gene birc5 exhibited distinct patterns in FW and SW, suggesting differential regulatory mechanisms in response to cold exposure. Transcriptomic analysis revealed that cold stress significantly influenced genes related to ion regulation, osmoregulation, and cellular metabolism, with distinct pathways activated in FW and SW environments. Notably, SW-specific genes were predominantly involved in metabolic pathways and stress signaling, while FW-specific genes were linked to transport processes and cellular maintenance. Additionally, cold stress significantly affected the expression of Na+/K+-ATPase (NKA) subunits and ion transport genes, underscoring the impact of temperature and salinity on gill function. The study highlights the importance of tight junctions (TJ) and gap junction (GJ) in maintaining gill integrity during environmental stress, with differential regulation of key genes like ocln, cask, and gja3 in response to salinity and temperature shifts. These findings highlight the superior molecular and cellular adaptations of euryhaline fish in SW to cold stress, emphasizing how salinity enhances gill responses and suggesting potential strategies for improving cold tolerance in aquaculture.

ALYREF regulates the m5C modification and stability of BIRC5 mRNA to promote ovarian cancer progression.

While normal cells are highly regulated, cancer cells take a dysregulated path which bolsters their survival. Currently, a limited number of uniform treatments are available for cancer cure. Our goal was to deprive cancer cells of the key nutrient methionine and determine what effect it would have on cell death and alterations in DNA methylation of prostate cancer cells. PC3 and other cell lines were transfected with plasmid gene constructs for methionine gamma lyase deaminase (MEGL), a methionine-degrading enzyme, targeted for expression in the cytoplasm (cMEGL) or the nucleus (nMEGL). For assessing cell death due to MEGL-mediated methionine deprivation, a standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used. PC3, and DU145 prostate cancer cells were selected for whole-methylome sequencing to determine the effects of MEGL expression. Key gene products comprising the Prolaris Molecular Score, specifically 31 cell-cycle progression genes, were chosen for assessing putative differences in methylome. Treatment with MEGL gene targeted for expression in either the cytoplasm or nucleus caused significant cell death, similar to that due to the anticancer drug methotrexate. Azacytidine showed no effect on PC3 cell death. Propargylglycine, an inhibitor of MEGL, prevented cell death. Methylome analysis showed increased methylation of two genes: Spindle and kinetochore-associated complex subunit 1 (SKA1), origin recognition complex subunit 6 (ORC6L), and reduced methylation of six promoters: BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B), PDZ binding kinase (PBK), baculoviral IAP repeat-containing 5 (BIRC5), centromere protein M (CENPM), DNA topoisomerase II alpha (TOP2A), minichromosome maintenance 10 replication initiation factor (MCM10), upon forced expression of MEGL. Methionine deprivation through MEGL-targeted gene therapy may be a viable option for inducing cancer cell death compared to unrestricted levels of methionine.

Lung cancer stands as one of the most prevalent malignancies globally, with its high morbidity and mortality intimately associated with its inconspicuous early symptoms, the advanced stages at diagnosis, and resistance to conventional therapeutic interventions. Exosomes, serving as pivotal mediators of intercellular communication, carry biomolecules that play crucial roles in tumorigenesis, progression, and metastasis, holding promise as novel targets for early diagnosis, prognostic evaluation, and treatment of lung cancer. In this study, lung cancer-related datasets were obtained from the GEO database and TCGA. Through differential gene analysis, enrichment analysis, immune infiltration analysis, and drug regulatory analysis, exosome-associated genes pertinent to lung cancer were screened and identified. The research revealed significant downregulation of CRYAB, CAV1, HYAL1, and TUBB6 genes in lung cancer tissues, whereas SERINC2, PAICS, SLC2A1, and BIRC5 genes were markedly upregulated. These genes were predominantly enriched in biological processes such as cell migration, oxidative stress response, and cell cycle regulation, as well as in KEGG pathways like the IL-17 signaling pathway. Immune infiltration analysis demonstrated a high correlation between these genes and the infiltration levels of various immune cells. Furthermore, through drug-gene enrichment analysis and molecular docking experiments, significant correlations were found between drugs such as celecoxib and some exosome-related genes, with interaction targets existing between these drugs and CAV1, SLC2A1, and BIRC5 genes. This study unveils the expression characteristics and biological significance of exosome-associated genes in lung cancer. The differential expression of these genes not only offers potential biomarkers for early diagnosis of lung cancer but also lays a foundation for further research into their biological functions in this disease.

ABSTRACTSalpingitis is a highly prevalent disease that reduces production performance and egg quality in laying hens, severely impeding the sustainable development of the egg‐laying industry. Fructooligosaccharides (FOS) play a significant role in regulating gut health and immune function. However, the mechanisms by which FOS alleviates salpingitis remain unclear. This study aimed to elucidate how FOS mitigates salpingitis using multi‐omics approaches. A total of 270 34‐week‐old Hy‐Line Brown laying hens were randomly assigned to three groups: a control group with a basal diet (CN), a lipopolysaccharide (LPS)‐challenged group on a basal diet (CN_LPS), and an FOS‐supplemented group (1 g/kg diet) with LPS challenge (FOS_LPS). The results showed that the supplementation of FOS significantly ameliorated LPS‐induced inflammation and atrophy in the magnum of hens (p < 0.05). The mRNA expression levels of TLR2, MYD88, NF‐κB, and COX2 in the FOS_LPS group were significantly reduced in the magnum compared to the CN_LPS group (p < 0.05). In contrast, the expression of ABCA9, BIRC5, and MYRF genes was significantly higher in the FOS_LPS group than in the CN_LPS group. Compared to the CN_LPS group, the FOS_LPS group exhibited a reduction in the abundance of Rikenellaceae_RC9_gut_group and Alistipes, whereas the abundances of Lactobacillus, Ruminococcus_torques_group, and Phascolarctobacterium were increased in cecal chyme. In addition, the FOS_LPS group exhibited elevated relative concentrations of S‐lactoylglutathione and thymol sulfate in plasma as compared to the CN_LPS group. Collectively, FOS mitigated LPS‐induced salpingitis by modulating key inflammatory pathways, restoring gut microbiota (e.g., increased Lactobacillus, decreased Rikenellaceae), and enhancing metabolic homeostasis.

Breast cancer is the most common cancer and the leading cause of cancer-related death in women. Differential gene expression can help identify genes involved in carcinogenesis or serve as biomarkers. This study provides a comprehensive evaluation of the gene expression focusing on apoptosis-related genes, in invasive breast carcinoma of no specific type compared with benign tissue. The gene expression of nine candidate genes identified as potential targets of certain microRNAs suggested as biomarkers and known for their role in apoptosis, and two additional apoptosis-related genes identified in the screening was evaluated using qPCR together with external datasets. Screening of 92 apoptosis-related genes identified several dysregulated genes including downregulated BCL2L2 and upregulated BIRC5 genes, which were further confirmed as tumor suppressor and as an oncogene, respectively. Among the miRNA-related genes, HMGA2 and RAB22A were overexpressed, while ATF2, PPM1L, VPS4A, ZEB1, and ZFP36L1 were underexpressed. The BIRC5/BCL2L2 gene signature provided AUC of 0.975, sensitivity of 93.10% and specificity of 96.43%. Increased BIRC5 expression was associated with higher tumor grades and Ki-67-positive samples while decreased levels of BCL2L2 were associated with Ki-67-positive samples. Luminal A and B samples were distinguished by the differential expression of these two genes. The high expression of HMGA2 and BIRC5 genes was observed as a negative prognostic factor for both overall survival (OS) and progression-free survival (PFS) with a favorable OS difference of ~ 1 year for HMGA2 and 1.2 years for BIRC5 in the case of their low expression. External validation identified ZEB1 as a positive and BIRC5 as a negative prognostic factor for both overall and disease-free survival. The results highlighted genes with possible roles in apoptosis and acting in breast carcinogenesis. In particular, BIRC5 was shown as important oncogene and ZEB1 as a tumor suppressor in invasive breast cancer. Further studies are warranted to evaluate the potential of the investigated genes as biomarkers or therapeutic targets, with possible implications for breast cancer diagnosis and treatment.

Molecular events that drive endometriosis (EM) and cause accompanying immune deregulation remain elusive. Our purpose was to identify key pathways involved in lesion formation across diverse populations and to detect transcriptomic changes in eutopic endometrium that accompany EM. We searched Gene Expression Omnibus and ArrayExpress and performed differential gene expression analysis and a network meta-analysis on nine qualifying datasets. Those contained transcriptomic data on 114 ectopic endometrium samples (EL), 138 eutopic endometrium samples from women with endometriosis (EEM), and 79 eutopic endometrium samples from women without endometriosis (EH). Gene ontology and enrichment analysis were performed in DAVID, Metascape, and Cytoscape, and drug repurposing was done in CMap. EEM compared to EH upregulated CCL21 and downregulated BIRC3, CEL, and LEFTY1 genes (|log2FC| > 0.5, p < 0.05). EL showed increased expression of complement and serpin genes (EL vs. EEM: C7, logFC = 3.38, p < 0.0001; C3, logFC = 2.40, p < 0.0001; SERPINE1, logFC = 1.02, p < 0.05; SERPINE2, logFC = 1.54, p < 0.001) and mast cell markers (EL vs. EEM: CPA3, logFC = 1.54, p < 0.0001; KIT, logFC = 0.74, p < 0.001). Functional enrichment analysis highlighted complement and coagulation, inflammation, angiogenesis, and extracellular matrix remodeling as drivers of endometriosis. Pharmacogenomic analysis indicated Janus kinase (JAK), cyclin-dependent kinase (CDK), and topoisomerase inhibitors as therapy targets. Our results suggest an interplay between complement and coagulation, mast cells, extracellular matrix remodeling, and the JAK/STAT3 pathway in endometriosis. We underscore the significance of complement C3 and propose JAK inhibitors as therapy candidates. Detected expression differences between EEM and EH are important for the development of diagnosis via endometrial biopsy.

BackgroundChronic Obstructive Pulmonary Disease (COPD) is chronic respiratory disease that severely affects patients’ quality of life and is associated with high mortality rates. Investigating the imbalance between regulatory T cells (Tregs) and T helper 17 cells (Th17) in COPD treatment is crucial, as this imbalance plays a significant role in the disease’s inflammatory processes. This study explores the therapeutic potential of the traditional Chinese medicine(TCM) formula, Lijin Fang (LJF), focusing on its ability to restore Treg/Th17 balance.MethodsWe employed bioinformatics and in vitro cell experiments to analyze the active components and targets of LJF. Network pharmacology, differential gene expression, pathway enrichment, ROC model prediction, and immune infiltration analyses were conducted, followed by molecular docking studies. Rat peripheral blood mononuclear cells (PBMCs) were cultured and treated with cigarette smoke extract (CSE) and LJF-containing serum, with flow cytometry, ELISA, and Western blotting used to assess relevant markers.ResultsOur findings demonstrate that treatment with (10% or 30%)LJF-containing serum significantly increased the proportion of Treg cells while concurrently decreasing Th17 cell populations in the 5%CSE-treated rat PBMC model (p<0.001). We observed a reduction in pro-inflammatory cytokines such as interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β), alongside an increase in the anti-inflammatory cytokine interleukin-10 (IL-10) (p<0.001). Additionally, potential therapeutic targets, including IL-10, potassium voltage-gated channel subfamily N member 4 (KCNN4), and Baculoviral IAP repeat-containing protein 3 (BIRC3), were identified. Molecular docking results indicated stable interactions between IL-10 and BIRC3 with the constituents of LJF.ConclusionThis study highlights LJF’s anti-inflammatory potential in restoring the Treg/Th17 balance and regulating cytokine expression in COPD.

Gut-testis axis in roosters: Lactiplantibacillus plantarum supplementation improves reproductive performance.

Breast cancer (BC) is a multifactorial disease, with genetic alterations in cell proliferation and migration pathways being significant risk factors. This study examines the association between three variants in the BIRC5 gene (rs8073069, rs17878467, and rs9904341) and breast cancer (BC) susceptibility. Peripheral blood DNA samples were collected from 423 women (221 BC patients and 202 healthy controls). Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) methodology. Associations were calculated using odds ratios (OR), with p-values adjusted by the Bonferroni test (significance at p ≤ 0.016). In silico analyses were conducted to predict the functional impact of the analyzed variants. Patients carrying the C/C genotype for the rs8073069 variant showed increased susceptibility to BC with early TNM (tumor-node-metastasis classification) stage and Luminal A subtype (OR > 2.00; p ≤ 0.004). For the rs17878467 variant, patients with the C/T or T/T genotype exhibited a higher susceptibility to developing breast cancer (BC), particularly at early TNM stages or with a histological lobular type (OR > 2.00; p ≤ 0.012). Regarding the rs9904341 variant, patients with the G/C or C/C genotype had a higher susceptibility to breast cancer. Notably, G/C genotype carriers with Luminal A and B subtypes, and C/C genotype carriers who had TNM stages II and III, and Luminal A, Luminal B, and HER2 subtypes demonstrated increased risk (OR > 2.00; p ≤ 0.009). The C-T-C haplotype (rs8073069-rs17878467-rs9904341) was significantly associated with BC (OR = 4.20; 95% CI = 2.38-7.41; p ≤ 0.001). In silico analysis using CADD indicated a low probability of deleterious effects. The results suggest that the rs8073069, rs17878467, and rs9904341 variants in BIRC5 have a significant influence on breast cancer susceptibility.

Prostate cancer is the second leading cause of cancer-related deaths in males that has an unfavorable outcome. Autophagy-related genes (ARGs) contribute to the process of tumorigenesis and metastasis of prostate cancer. This study aimed to identify ARGs that could serve as reliable and non-invasive biomarkers for evaluating prostate cancer prognosis. The expression profiles of ARGs were identified in prostate cancer specimens with good prognosis (n = 98) and poor prognosis (n = 42). A series of in vitro assays were performed to explore the function and mechanisms of ARGs in malignant progression of prostate cancer. Receiver operating characteristic curve were utilized to evaluate the predictive potential of ARGs for prostate cancer prognosis. Patients with poor prognosis exhibited higher expression of baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) and lower expression of neuregulin 2 (NRG2) compared to those with good prognosis. BIRC5 served as independent risk factors for prostate cancer prognosis, and enhanced BIRC5 expression promoted cells viability, migration, and invasion, but the autophagy activator rapamycin could counteract the effects of the BIRC5 gene. Conversely, NRG2 acted as a protective factor for prostate cancer prognosis, and elevated NRG2 expression suppressed cells viability, migration, and invasion, but the autophagy inhibitor 3-Methyladenine could reverse the effects of the NRG2 gene. The combination of BIRC5, NRG2 with prostate specific antigen (PSA) demonstrated significant predictive value for prostate cancer prognosis. BIRC5 and NRG2 genes participate in the progression of prostate cancer by regulating autophagy. BIRC5 and NRG2 have the potential to serve as valuable biomarkers for the prognosis of prostate cancer.

Purpose: Analysis of PMAIP1 and BIRC5 gene expression in breast cancer cells after proton exposure, both as monotherapy and in combination with doxorubicin. Material and methods: The object of the study was MCF-7 cells. Four study groups were formed: a group exposed to ionizing radiation; a group treated with doxorubicin; a group of combined exposure to ionizing radiation and doxorubicin; and an untreated control group. The cells were irradiated at the Prometheus proton radiation complex at the A.F. Tsyb MRSC, with a scanning proton beam at a dose of 4 Gy (proton energy of 100 MeV) in the center of the distributed Bragg peak. The cells were treated with the chemotherapy drug doxorubicin at a concentration of 0.004 mg/ml 24 hours before irradiation. Total RNA was isolated using an RNA Solo kit and quantified spectrophotometrically (NanoDrop ND-1000). Reverse transcription and amplification were performed simultaneously in real time using the OneTube RT-PCR kit with SYBR Green I as a fluorescent indicator. Results: The analysis showed that doxorubicin suppresses the expression of BIRC5 (up to 0.02), which is consistent with its known apoptogenic activity. However, the combined effect of doxorubicin and radiation leads to an increase in BIRC5 expression (up to 0.63) and a simultaneous decrease in PMAIP1 expression (up to 0.0003). This indicates the launch of complex compensatory cell survival mechanisms aimed at suppressing apoptosis and enhancing DNA repair under conditions of combined cytotoxic stress. A less pronounced decrease in BIRC5 expression during ionizing radiation monotherapy (up to 0.16) compared with doxorubicin (0.02) is probably due to differences in the nature and kinetics of DNA damage induced by these agents. The data obtained indicate the nonlinear nature of the cellular response to combined exposure and emphasize the difficulty of predicting the effectiveness of combined radiotherapy. Conclusion: The results demonstrate the antagonistic interaction of doxorubicin and ionizing radiation in the regulation of apoptosis in MCF-7 cells, emphasizing the need for further research to optimize combination cancer therapy.

BackgroundGemcitabine (GEM) is used as a first-line therapy for patients diagnosed with any stage of pancreatic cancer (PC); however, patient survival is poor because of GEM resistance. Thus, new approaches to overcome GEM resistance in PC are urgently needed. Here, we aimed to establish an in vivo drug-resistant PC model and identify genes involved in GEM resistance. We focused on one of these factors, CITED4, and elucidated its mechanisms of action in GEM resistance in PC.MethodsL3.6pl, a GEM-sensitive PC cell line, was orthotopically injected into the pancreas of BALB/c nude mice to establish a GEM-resistant PC animal model. Transcriptomic data from control or GEM-resistant tumor-derived cells were analyzed. GEM resistance was evaluated using cell viability, clonogenicity, and apoptosis assays. An apoptosis array was used to identify genes downstream of CITED4. A CITED4 knockout-mediated GEM sensitivity assay was performed in an orthotopic xenograft mouse model using PANC-1 cells, which are GEM-resistant cells.ResultsFrom the RNA sequencing data of isolated GEM-resistant PC cells and The Cancer Genome Atlas dataset, 15 GEM resistance-related genes were found to be upregulated, including CITED4, the gene encoding a type of CBP/p300-interacting transactivator implicated in several cancers. CITED4 knockdown in drug-resistant cells reduced cell proliferation and migration but increased apoptosis. To identify the molecular mechanism underlying CITED4-mediated induction of GEM resistance, alterations in Baculoviral IAP Repeat Containing 2 (BIRC2) levels were observed using an apoptosis array. BIRC2 expression was downregulated following CITED4 knockdown in GEM-resistant PC cell lines. Furthermore, chromatin immunoprecipitation and promoter assays showed that BIRC2 was directly regulated by CITED4. Consistent with the CITED-knockdown experiments, silencing of BIRC2 increased the sensitivity of L3.6pl-GEM-resistant and PANC-1 cell lines to GEM. Furthermore, CITED4 knockout using the CRISPR-Cas9 system in PANC-1 cells increased the sensitivity to GEM in orthotopic mice. Moreover, elevated CITED4 and BIRC2 expression levels were associated with poorer outcomes in human PC clinical samples.ConclusionsCollectively, these results indicate that CITED4 regulates GEM resistance via inhibition of apoptosis by upregulating BIRC2 expression in PC cells. Therefore, CITED4 may serve as a valuable diagnostic marker and therapeutic target for GEM-resistant PC.

Colorectal adenocarcinoma (COADREAD) is the second most common cause of cancer-associated deaths. Immunity and autophagy play a key role in the development and progression of COADREAD, but the specific mechanisms have not been fully elucidated. We aimed to explore immune- and autophagy-related genes (IARGs) to establish prognostic risk assessment and clinical prediction models and to understand the molecular basis of COADREAD. Transcriptomic and clinical data from colon (COAD) and rectal cancers (READ) were obtained from TCGA and GEO databases, including 460 COADREAD cases and validation cohorts (GSE161158/GSE17536). Immune-related (IRGs) and autophagy-related genes (ARGs) were integrated to identify 22 immune-autophagy-related genes (IARGs). Molecular subtypes were constructed via consensus clustering of IARGs, followed by gene set variation analysis (GSVA) to explore pathway activity. Differentially expressed immune-autophagy-related genes (IARDEGs) were identified using limma and subjected to functional enrichment [Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG)]. A prognostic risk model was developed via LASSO and Cox regression, validated in external cohorts. Immune infiltration was assessed using ssGSEA, and a nomogram integrating clinicopathological features was established. Statistical analyses were performed in R (v4.2.2), with significance at P<0.05. The IARG data could be used to distinguish between cancerous and normal specimens of COADREAD. VEGFA, BIRC5, and BID genes were highly expressed in COADREAD, while the expression of TNFSF10 was low. Most of the IARGs were positively correlated with COADREAD. The GSVA results of four classes of C4 verified that the clustering effect was best. More IARGs, such as CXCR4, CCL2, and CTSB, were in the C4 class than the C1 class. In the risk model, the T cell and B cell receptor pathways were substantially upregulated in patients in the low-risk group. The risk score greatly differed with the different expression levels of key immune checkpoints and immune cell infiltration, and the levels of immune cells were higher in the low-risk group. In this study, bioinformatic analysis proved that immune-a1-related genes could be used to distinguish between normal and COADREAD specimens and that immunity and autophagy are associated with low-risk COADREAD; therefore, these genes have the potential to improve clinical predictions of COADREAD risk.

Shear stress preconditioning enhances periodontal ligament stem cell survival.

Survivin (BIRC5) is an anti-apoptosis protein over expressed in most cancers and associated with poor clinical outcomes. We have provided an updated meta-analysis of -31G/C (rs9904341) gene polymorphism which is highly associated with cancer risk. A comprehensive literature search in PubMed and Google Scholar databases was conducted. A total of 10472 cases and 12193 controls from 51 studies were included in this meta-analysis. This study was prospectively registered in PROSPERO, and sensitivity analysis, risk of bias analysis, and statistical analysis were performed. A pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the strength of the association. All analyses were achieved using RevMan 5.4 software and Excel 2013 version. The overall meta-analysis indicates that survivin gene polymorphism -31G/C (rs9904341) is highly associated with overall cancer risk in allelic (C vs. G, OR=1.25,95% CI= 1.15 to 1.37, P<0.00001), homozygous co-dominant (CC vs. GG, OR=1.53, 95% CI= 1.23 to 1.90, P=0.0001), heterozygous co-dominant (CC vs. CG, OR= 1.34, 95% CI= 1.18 to 1.52, P<0.00001), dominant model(CC+CG vs. GG, OR= 1.29, 95% CI= 1.14 to 1.46, P= <0.0001) and recessive model (CG+GG vs. CC, OR= 0.70, 95% CI= 0.61 to 0.81, P<0.00001). The stratified analysis revealed that the variant significantly increases the risk in the Asian population. -31G/C (rs9904341) polymorphism of the BIRC5 gene is associated with the risk of cancer in the Asian population. However, further large-scale clinical studies are required to re-evaluate this result in the future.

Long noncoding RNA (lncRNA) TEX41 has been linked to the progression of various kinds of cancers. In this study, the expression of lncRNA TEX41 and cell biological function of lncRNA TEX41 were examined in the context of hepatocellular carcinoma (HCC) to measure their ability to predict HCC progression. The relationship between lncRNA TEX41, miR-200a-3p, and potential downstream target gene BIRC5 was further explored. The purpose of the present study was to provide a new theoretical basis for the diagnosis and treatment of HCC. The GEPIA2, starBase and Gene Expression Omnibus (GEO) databases were used to analyze the biological functions and molecular mechanisms of lncRNA TEX41. The expression of lncRNA TEX41 in clinical tissue samples and cell lines was detected via quantitative real-time polymerase chain reaction (qRT-PCR). We investigated the impact of TEX41 on the proliferation, migration, and invasion of HCC cells, as well as its underlying mechanism. The expression levels of lncRNA TEX41 in HCC tissues are higher than those in adjacent tissues. The expression of lncRNA TEX41 was associated with lymph node metastasis and tumor-node-metastasis (TNM) staging in HCC patients. Silencing lncRNA TEX41 inhibited the proliferation, migration, and invasion of HCC cell lines. Low expression of lncRNA TEX41 may have affected epithelial-mesenchymal transition (EMT) in HCC cell lines. There may be a functional relationship between lncRNA TEX41 and miR-200a-3p-BIRC5. LncRNA TEX41 may promote the progression of HCC through the miR-200a-3p-BIRC5 axis.

Abstract Background: Recently, immune checkpoint inhibitors (ICIs) have been increasingly applied in the treatment of small cell lung cancer (SCLC). While their development has enhanced treatment options for SCLC, the effectiveness of immunotherapy remains limited due to the low expression of Programmed Cell Death Ligand 1 (PD-L1) and the emergence of immunotherapy resistance. As a result, there is a pressing need for new biomarkers to guide SCLC treatment. Methods: We obtained four microarray datasets from GEO (Gene Expression Omnibus) database and screened differentially expressed genes (DEGs). After the establishment of protein-protein interaction network through Cytoscape, key hub genes were selected via a volcano plot. To validate these results, we used an independent dataset as a test cohort. We also analyzed differences in immune cell infiltration between normal and SCLC samples. Lastly, we identified a marker gene associated with immune cell infiltration and validated its role in SCLC through in vitro experiments. Results: We screened GEO gene expression database for DEGs, which are immune-related genes, in SCLC. A PPI network analysis revealed seven overexpressed hub genes (AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, AURKA) in the SCLC cohort, which were significantly more expressed than in normal cells. Correlation analysis between immune cells and the seven hub genes showed that BIRC5 expression was inversely correlated with monocytes. In SCLC cell lines such as SBC5 and SBC3, downregulation of BIRC5 using siRNA induced apoptosis and inhibited cell activity, tumor invasiveness and proliferative potential. Furthermore, treatment with a BIRC5 inhibitor (YM155) reduced SCLC cell viability and increased apoptosis. Co-culture experiments with SBC3 and monocytes (e.g., THP1) led to decreased BIRC5 expression in SBC3 cells. Conclusion: We identified AURKB, BIRC5, TOP2A, TYMS, PCNA, UBE2C, and AURKA genes as potential immune-related therapeutic targets for SCLC. In particular, high BIRC5 expression promotes SCLC progression and may influence the immune microenvironment of the tumor by affecting monocytes. Citation Format: Akihiko Miyanaga, Yang Yunchu, Kuniko Matsuda, Takehiro Tozuka, Aya Fukuizumi, Kakeru Hisakane, Naomi Onda, Susumu Takeuchi, Koichiro Kamio, Kazuo Kasahara, Masahiro Seike. Immune-associated genes as potential therapeutic targets in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5687.