Background: Ovarian cancer (OC) is a high-mortality gynecological cancer that is typically treated with cisplatin, although such treatment often results in chemoresistance. Ovarian cancer resistance is usually related to cell stemness. Herein, we explored the function of lncRNA WDFY3-AS2 in OC cell resistance to cisplatin (DDP). Methods: Cisplatin resistant OC A2780 cell lines (A2780-DDP) were established by long-term exposure to cisplatin. CCK-8 assay were performed to evaluate the viability of A2780, and A2780-DDP cells. Quantitative RT-PCR was used to examine the expression of lncRNA WDFY3-AS2, miR-139-5p, and SDC4 in A2780-DDP cell lines. After treatment with cisplatin, cell apoptosis and CD44⁺CD166⁺-positive cells were measured by flow cytometry. The transwell assays were employed to measure the effect of WDFY3-AS2 on cell migration, and invasion. In addition, tumorsphere formation assay was used to enrich OC cancer stem cells (CSCs) from A2780-DDP cells. The expression of CSC markers (SOX2, OCT4, and Nanog) was detected by western blotting. The regulatory mechanism was confirmed by RNA pull down, and luciferase reporter assays. Furthermore, xenograft tumor in nude mice was used to assess the impact of WDFY3-AS2 on cisplatin resistance in OC in vivo. Results: WDFY3-AS2 was highly expressed in OC A2780-DDP cells, and silencing WDFY3-AS2 significantly inhibited proliferation, migration and invasion but increased apoptosis in OC A2780-DDP cells. Additionally, WDFY3-AS2 significantly promoted the A2780-DDP cells tumorspheres. WDFY3-AS2 was predicted to impact OC by sponging miR-139-5p and regulating SDC4. The xenografts inoculated with A2780-DDP cells additionally confirmed that tumor growth in vivo was reduced by si-WDFY3-AS2 transfection. MiR-139-5p inhibitor or SDC4 overexpression could restore the suppressive influence of silenced WDFY3-AS2 on tumor growth. Conclusions: Together, WDFY3-AS2 may lead to change of cisplatin resistance by the expression of miR-139-5p/SDC4 in the OC A2870-DDP cells both in vitro and in vivo. Our finding may provide a drug target for the drug resistance of OC.

Cancer growth is significantly influenced by processes such as pyroptosis, apoptosis, and necroptosis that underlie PANoptosis, a proinflammatory programmed cell death. Several studies have examined the long non-coding RNAs (lncRNAs) associated with pancreatic adenocarcinoma (PAAD). However, the predictive value of lncRNAs related to PANoptosis for PAAD has not been established. The Clinical Genome Atlas database was used to obtain the transcriptome 、clinical data and the corresponding mutation data of the patients with PAAD in this study. The least absolute shrinkage and selection operator regression analysis was employed to obtain prognosis-related lncRNAs for constructing a risk signature. According to the median risk score of the signature, patients with PAAD were grouped into low- and high-risk groups to further compare the survival prognosis of different risk groups. Time-dependent receiver operating characteristic curves, c-index analysis, nomograms, principal component analysis and univariate Cox and multivariate Cox regression were performed for the internal validation of the signature. In addition, enrichment analysis of different genes was performed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Lastly, differences in tumor mutation burden (TMB), immune function, tumor immune dysfunction and rejection (TIDE), and drug response were determined for the two risk groups. The signature was constructed with six PANoptosis-related lncRNAs (AC067817.2、LINC02004、AC243829.1、AC092171.5、AP005233.2、AC004687.1) that predicted the prognosis of the patients with PAAD. Survival curves showed that patients in the two risk groups had statistically significant differences in prognosis (P < 0.05), and multi-cox regression analysis identified risk score as an independent risk factor for PAAD prognosis, and internal validation of nomograms showed high confidence in the signature. GO and KEGG enrichment analysis showed functional and pathway differences between the high- and low-risk groups. TMB evaluation demonstrated that patients in the high-risk group had a higher frequency of mutations. The TIDE score indicated that the high-risk group had a lower risk of immunotherapy escape and better immunotherapy outcomes. Additionally, the two risk groups revealed significantly different responses to 11 anticancer drugs. We identified a novel risk signature for PANoptosis-related lncRNAs, which is a standalone prognostic indicator for PAAD. The PANoptosis-related lncRNA risk signature may be relevant for immunotherapy and a therapeutic target for PAAD.

Vasculogenic mimicry (VM) with the pattern of endothelial independent tubular structure formation lined by aggressive tumor cells mimics regular tumor blood vessels to ensure robust blood supply and correlates with the proliferation, invasion, metastasis, and poor prognosis of malignant tumors, which was demonstrated to be a major obstacle for resistance to antiangiogenesis therapy. Therefore, it is urgent to discover methods to abrogate the VM formation of tumors, which possesses important practical significance for improving tumor therapy. Brucine is a traditional medicinal herb extracted from seeds of Strychnos nux-vomica L. (Loganiaceae) exhibiting antitumor activity in a variety of cancer models. In the present study, the effect of brucine on vasculogenic mimicry and the related mechanism are to be investigated. We demonstrated that, in a triple-negative breast cancer cell line MDA-MB-231, brucine induced a dose-dependent inhibitory effect on cell proliferation along with apoptosis induction at higher concentrations. The further study showed that brucine inhibited cell migration and invasion with a dose-dependent manner. Our results for the first time indicated that brucine could disrupt F-actin cytoskeleton and microtubule structure, thereby impairing hallmarks of aggressive tumors, like migration, invasion, and holding a possibility of suppressing vasculogenic mimicry. Hence, the inhibitory effect of brucine on vasculogenic mimicry was further verified. The results illustrated that brucine significantly suppressed vasculogenic mimicry tube formation with a dose-dependent effect indicated by the change of the number of tubules, intersections, and mean length of tubules. The in-depth molecular mechanism of vasculogenic mimicry suppression induced by brucine was finally suggested. It was demonstrated that brucine inhibited vasculogenic mimicry which might be through the downregulation of erythropoietin-producing hepatocellular carcinoma-A2 and matrix metalloproteinase-2 and metalloproteinase-9.

This study developed a prognostic signature for cervical cancer using transcriptome profiling and clinical data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and TISCH database, focusing on cancer-associated fibroblasts (CAFs). Through LASSO Cox regression and integrated bioinformatics analyses, we identified 144 differentially expressed genes (DEGs) related to CAFs, from which an 11-gene CAF-related signature (CAFRSig) was constructed. The CAFRSig effectively stratified patients into high- and low-risk categories, demonstrating significant prognostic capability in predicting overall survival. Gene ontology (GO) and gene set variation analysis (GSVA) linked the DEGs to crucial pathways in tumor malignancy, immune response, and fatty acid metabolism. The immune landscape analysis, utilizing the TIMER platform and CIBERSORT algorithm, revealed a positive correlation between immune cell effector functions and CAFRSig scores, highlighting the model's potential to identify patients likely to respond to immune checkpoint blockade (ICB) therapies. Furthermore, neuropilin 1 (NRP1), a key gene in the CAFRSig, was upregulated in cervical cancer tissues and associated with disease progression and differentiation. The downregulation of NRP1 curbed cell proliferation and influenced the epithelial-mesenchymal transition (EMT), implicating the PI3K/AKT pathway and modulating PD-L1 expression. This comprehensive analysis establishes a robust prognostic signature based on CAF-related genes, offering valuable insights for optimizing therapeutic strategies in cervical cancer management.

Cancer-associated fibroblasts (CAFs) play a role in ovarian cancer (OV) evolution, immunosuppression and promotion of drug resistance. Exploring the value of CAFs-related biomarker in OV is of great importance. In the present work, we developed a CAFs-related index (CAFRI) based on an integrated analysis of single-cell and bulk RNA-sequencing and highlighted the value of CAFRI in predicting clinical outcomes in individuals with OV, tumour immune microenvironment (TIME) and response to immune checkpoint inhibitors (ICIs). The GSE151214 cohort was used for cell subpopulation localization and analysis, the TCGA-OV patients as a training set. Moreover, the ICGC-OV, GSE26193, GSE26712 and GSE19829 cohorts were used for the validation of CAFRI. The TIMER 2.0, CIBERSORT and ssGSEA algorithms were used for analysis of TIME characteristics based on the CAFRI. The GSVA, GSEA, GO, KEGG and tumour mutation burden (TMB) analyses were used for mechanistic exploration. Additionally, the IMvigor210 cohort was conducted to validate the predictive value of CAFRI on the efficacy of ICIs. Finally, CAFRI-based antitumour drug sensitivity was analysed. The findings demonstrate that the CAFRI can served as an excellent predictor of prognosis for individuals with OV, as well as identifying patients with different TIME characteristics, differentiating between immune ‘hot’ and ‘cold’ tumour populations, and providing new insights into the selection of ICIs and personalised treatment regimens. CAFRI provides new perspectives for the development of novel prognostic and immunotherapy efficacy predictive biomarkers for OV.