Yaoxian Wang

Cellular mechanical properties play a critical role in physiological and pathological processes, with fluid shear stress being a key determinant. Despite its importance, the impact of fluid shear stress on the mechanical characteristics of HeLa cells and its role in the mechanism of tumor metastasis remain poorly understood. This study aims to investigate the effects of varying durations of fluid shear stress on the mechanical properties of HeLa cells, thereby elucidating the mechanical interactions between the fluid flow environment and cancer cells during tumor metastasis. We established an in vitro fluid shear stress cell experimental system and analyzed the flow field characteristics within a parallel plate flow chamber using computational fluid dynamics software. Atomic force microscopy was used to measure the mechanical properties of HeLa cells at different time points under a fluid shear stress of 10 dyn/cm², a value representative of physiological conditions. computational fluid dynamics analysis confirmed the stability of laminar flow and the uniformity of shear stress within the parallel plate flow chamber. The experimental results revealed that with increasing fluid shear stress exposure duration, HeLa cells exhibited a fusiform shape, with a reduction in cell height and a significant decrease in cell Young’s modulus. By integrating atomic force microscopy with the in vitro fluid shear stress cell experimental system, this study demonstrates the substantial influence of fluid shear stress on the mechanical properties of HeLa cells. This provides novel insights into the behavior of cancer cells within the in vivo flow environment. Our findings enhance the understanding of cellular mechanical property regulation and offer valuable insights for biomedicine engineering research.

Artemisia annua L. (A. annua), a Traditional Chinese Medicine (TCM) that has been utilized in China for centuries, is known for its potential anticancer properties. However, the main components and mechanism of action of A. annua on endometrial carcinoma have not been reported. We used the TCMSP database to identify the active components of A. annua and their corresponding gene targets. We then obtained the gene targets specific to endometrial cancer from The Cancer Genome Atlas (TCGA) and GeneCards databases. The gene targets common to three databases were selected, and a "component-target" network was constructed. Protein-protein interaction (PPI) network analysis and ranking of the target proteins identified the key protein PTGS2 network analysis, and ranking of the target proteins identified the key protein PTGS2. We also screened the active components of A. annua and found that quercetin, kaempferol, luteolin, isorhamnetin, artemisin, and stigmasterol had the most targets. Molecular docking models were established for these six components with PTGS2, revealing strong binding activity for all of them. Finally, we conducted validation experiments to assess the effects of quercetin, an active component of A. annua, on endometrial cancer cells (HEC-1-A and Ishikawa cells). Our findings demonstrate that quercetin has the potential to inhibit both cell growth and migration, while also suppressing the expression of PTGS2.

High-grade serous ovarian cancer (HGSOC) is a common subtype of ovarian cancer with high mortality. Finding a new biomarker is useful for the diagnosis and treatment of HGSOC. The scRNA and bulk RNA data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. The monocyte-related clusters were identified and annotated by Seruat and SingleR package. The Kaplan–Meier and receiver operating characteristic curve was used to determine the prognosis. The differentially expressed genes were determined by limma. The single sample Gene Set Enrichment Analysis, Gene Set Enrichment Analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes were used for the enrichment function. The correlation between drug activity and gene expression was assessed by rcellminer and rcellminer Data package. We identified 9 cell types and obtained 37 differentially expressed marker genes of monocyte. A2M, CD163, and FPR1 were screened out as hub genes and used to construct risk model in HGSOC through univariate and multivariate cox analysis. Single sample Gene Set Enrichment Analysis showed risk score was related to B cell and T cell signal pathways, and further analysis showed most immune checkpoint genes expressions were upregulated in high-risk score group. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis exhibited that hub gene related genes were involved in signal receptor binding and cytokine-cytokine interaction. Low A2M expression and high expression of CD163 and FPR1 were associated with poor prognosis. Gene Set Enrichment Analysis revealed that A2M promoted tumor development through enhancing immune cell related signal pathways, while CD163 and FPR1 inhibited tumor development through activated carcinogenic signal pathways. Drug sensitivity analysis revealed that these hub genes could be potential therapeutic targets for the treatment of HGSOC. We constructed a risk model for the overall survival and explored the potential mechanism of monocyte in HGSOC.

Background Angelica sinensis (Oliv.) Diels has been used for centuries in Chinese traditional medicine to treat gynecological ailments. Numerous studies indicate that Angelica sinensis polysaccharide (ASP), an extract from Angelica sinensis, can inhibit various forms of cancer. Nevertheless, the therapeutic potential of ASP for treating ovarian cancer remains largely unexplored. Methods The study investigated cell proliferation and invasion, as well as the effects of a combination of ASP and DDP after tumor formation in nude mice. Tumor size was monitored, and HE staining was conducted on tissue samples. The identification of key gene GPX4 was performed via RNA-seq and bioinformatic analysis. GPX4 was overexpressed using lentivirus transfection, and its expression was evaluated via RT-qPCR and western blot. Additionally, the ferroptosis of cells was assessed through the measurement of Fe²⁺, malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Results The results indicated a synergistic effect of ASP combined with DDP, leading to better inhibition of proliferation and invasion of SKOV3/DDP cells. Similarly, ASP combined with DDP demonstrated tumor proliferation inhibition in tumor-forming nude mice, while maintaining good safety. Bioinformatics analysis of 843 differentially expressed genes (DEGs) revealed that the key gene GPX4 played a significant role in the mechanism of action. Furthermore, the expression of GPX4 was inhibited by ASP combined with DDP, which resulted in SKOV3/DDP inhibition of proliferation and invasion. The study also demonstrated that ASP combined with DDP led to increased levels of Fe²⁺ and MDA, while decreasing levels of GSH and SOD, suggesting the promotion ferroptosis of SKOV3/DDP cells. Conclusions The combination of ASP and DDP has the ability to inhibit the proliferation and invasion of SKOV3/DDP cells. Additionally, inhibiting GPX4 expression in SKOV3/DDP cells promotes ferroptosis.

Cervical cancer (CC) represents one of the most frequent gynecological tumors worldwide and it takes a big part in cancer-related deaths in women. The mouse double minute 2 (MDM2) gene has been elucidated to be deregulated in cancers and exert its oncogenic activity. Through ENCODE (https://www.encodeproject.org/), LOC100130075 was discovered to be a nearby gene of MDM2. Emerged as a novel long non-coding RNA (lncRNA), LOC100130075 has not been studied in cancers. Therefore, we aim to figure out the function of LOC100130075 and its interaction with MDM2 in CC progression. The high expression pattern of LOC100130075 and MDM2 and a positive correlation between them were firstly verified in CC cells. Then, it was verified that LOC100130075 interference suppressed the proliferation and enhanced the apoptosis of CC cells. Furthermore, we verified through mechanism assays including ChIP, RNA pull-down, as well as luciferase reporter assays that LOC100130075 bound to E2F transcription factor 1 (E2F1) to activate MDM2 transcription. Furthermore, the result of rescue assays manifested that MDM2 overexpression reversed the inhibitory function of LOC100130075 deficiency on CC development. In a word, LOC100130075 promoted CC malignancy by activating MDM2 transcription through E2F1, which may provide a new direction in the advancement of CC treatments.

This study aimed to synthesize silica-coated gold (Au@SiO2) nanoparticles coupled to antibodies against the scavenger receptor class B type I (SR-BI) and investigate their potential ability of visual tracking and treatment of cervical cancer. The fluorescein isothiocyanate (FITC)-labeled Au@SiO2-SR-BI antibody was synthesized, followed by characterization determination. The expression and location of SR-BI protein in cervical cancer cells were respectively detected by western blot and immunofluorescence assays. The effects of nanoparticles on cancer cells were determined by adsorption assay and apoptosis detection, respectively. The effects of nanoparticles on tumor formation in nude mice were determined. The particle sizes of Au@SiO2 ranged from 2-2.5 mu m, and the particle size distribution was relatively uniform. MS751 showed the highest expression of SR-BI. SR-BI was located in the cytomembrane. There were more FITC-Au@SiO2-SR-BI nanoparticles on the surface of the cells compared to FITCAu@SiO2. Significant apoptosis was observed in the FITC-Au@SiO2-SR-BI-treated group in both MS751 and H8 cells. Photothermal ablation of solid tumors was observed when FITC-Au@SiO2-SR-BI was activated using 808 nm wave. Expressions of the apoptosis-related markers including BCL2, BCLX, and p-AKT were significantly decreased, while those of caspase 3 and caspase 8 were significantly increased. The study presented a novel antibody-conjugated Au@SiO2 nanoparticle specifically targeting molecular receptors on cancer cell membranes. Antibody-conjugated Au@SiO2 nanoparticles may have therapeutic potential for the treatment of cervical cancer.

Purpose: The variation in inflammation in chronic obstructive pulmonary disease (COPD) between individuals is genetically determined. This study aimed to identify gene signatures of COPD through bioinformatics analysis based on multiple gene sets and explore their immune characteristics and transcriptional regulation mechanisms. Methods: Data from four microarrays were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes (DEGs) between COPD patients and controls. Weighted gene co-expression network analysis was applied to identify trait-related modules and then select key module-related DEGs. The optimized gene set of signatures was obtained using the least absolute shrinkage and selection operator (LASSO) regression analysis. The CIBERSORT algorithm and Pearson correlation test were used to analyze the relationship between gene signatures and immune cells. Finally, public databases were used to predict the transcription factors (TFs) and upstream miRNAs. Results: A total of 127 DEGs in COPD were identified from the combined dataset. By considering the intersection of DEGs and genes in two trait-related modules, 83 key module-related DEGs were identified, which were mainly enriched in interleukin-related pathways. Seven-gene signatures, including MTHFD2, KANK3, GFPT2, PHLDA1, HS3ST2, FGG, and RPS4Y1, were further selected using the LASSO algorithm. These gene signatures showed the predictive potential for COPD risks and were significantly correlated with 18 types of immune cells. Finally, nine miRNAs and three TFs were predicted to target MTHFD2, GFPT2, PHLDA1, and FGG. Conclusion: We proposed the seven-gene-signature to predict COPD risk and explored its potential immune characteristics and regulatory mechanisms.

Purpose Cervical cancer remains a major cause of cancer-related death in women, especially in developing countries. Previously, we found that the acetylation levels of chloride intracellular channel 1 (CLIC1) at lysine 131 were increased in cervical cancer tissues using a label-free proteomics approach. The aim of this study was to further determine the role of CLIC1 expression and its acetylation in cervical cancer. Methods CLIC1 expression and its implications for the prognosis of cervical cancer were analyzed using primary patient samples and cells, and the Gene Expression Profiling Interactive Analysis (GEPIA) database (gepia.cancer-pku.cn). The effect of CLIC1 on cervical cancer cells was evaluated using Cell Counting Kit (CCK)-8, flow cytometry, scratch wound healing, transwell, Western blotting and co-immunoprecipitation (Co-IP) assays. In vivo tumor growth was assessed using mouse xenograft models. Results We found that CLIC1 expression was increased in cervical cancer tissues and cells and that patients with a high CLIC1 expression tended to have a shorter overall survival time. Knockdown of CLIC1 significantly reduced in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumorigenesis. At the molecular level, we found that nuclear factor kappa B (NF-κB) activity was positively regulated by CLIC1. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-κB, attenuated the tumor-promoting effect of CLIC1. Moreover, we found that CLIC1 acetylation at K131 was upregulated in cervical cancer cells, which stabilized CLIC1 by inhibiting its ubiquitynation. Substitution of K131 inhibited CLIC1 ubiquitynation and promoted in vitro cervical cancer cell proliferation, migration and invasion, and in vivo tumor growth. In addition, we found that acetyltransferase HAT1 was responsible for CLIC1 acetylation at K131. Conclusion Our data indicate that CLIC1 acts as a tumor promoter in cervical cancer, suggesting a potential treatment strategy for cervical cancer by regulating CLIC1 expression and/or acetylation.

Background: Lysine acetylation is a post-translational modification that regulates a diversity of biological processes, including cancer development. Methods: Here, we performed the quantitative acetylproteomic analysis of three primary cervical cancer tissues and corresponding adjacent normal tissues by using the label-free proteomics approach. Results: We identified a total of 928 lysine acetylation sites from 1547 proteins, in which 495 lysine acetylation sites corresponding to 296 proteins were quantified. Further, 41 differentially expressed lysine acetylation sites corresponding to 30 proteins were obtained in cervical cancer tissues compared with adjacent normal tissues (Fold change > 2 and P < 0.05), of which 1 was downregulated, 40 were upregulated. Moreover, 75 lysine acetylation sites corresponding to 58 proteins were specifically detected in cancer tissues or normal adjacent tissues. Motif-X analysis showed that kxxxkxxxk, GkL, AxxEk, kLxE, and kkxxxk are the most enriched motifs with over four-fold increases when compared with the background matches. KEGG analysis showed that proteins identified from differently and specifically expressed peptides may influence key pathways, such as Notch signaling pathway, viral carcinogenesis, RNA transport, and Jak-STAT, which play an important role in tumor progression. Furthermore, the acetylated levels of CREBBP and S100A9 in cervical cancer tissues were confirmed by immunoprecipitation (IP) and Western blot analysis. Conclusions: Taken together, our data provide novel insights into the role of protein lysine acetylation in cervical carcinogenesis.