Background Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Deciphering the novel molecular mechanisms underlying stem-like traits may provide important insight for developing novel therapeutics. Methods Immunohistochemistry and immunofluorescence assays in prostatic tissues; gain- and loss-of-function analyses using ectopic overexpression and shRNAs in PCa cell lines; measurements of tumorigenic and stemness properties, and transcription in vitro and in vivo; transcriptional analysis in public databases. Results We identified that overexpression of BTF3 in PCa tissues and BTF3 expression highly correlates to stem-like traits. Cancer stem-like characteristics in PCa including self-renewal and metastatic potential were impaired by BTF3 loss and promoted by BTF3 overexpression. Mechanistically, BTF3 could stabilize BMI1, which is a crucial regulator of prostate stem cell self-renewal. More importantly, our data revealed that BTF3 is highly predictive of poor prognosis and may help in risk stratification of PCa patients. Conclusions BTF3 promotes PCa progression though modeling stem-like traits in PCa. BTF3 represents a stratification marker in PCa progression and outcomes. Electronic supplementary material The online version of this article (10.1186/s13046-019-1222-z) contains supplementary material, which is available to authorized users.

Ferroptosis is a novel form of regulated cell death trigged by various biological processes, and p53 is involved in different ferroptosis regulations and functions as a crucial regulator. Both DNA and RNA can fold into G-quadruplex in GC-rich regions and increasing shreds of evidence demonstrate that G-quadruplexes have been associated with some important cellular events. Investigation of G-quadruplexes is thus vital to revealing their biological functions. Specific G-quadruplexes are investigated to discover new effective anticancer drugs. Multiple modulations have been discovered between the secondary structure G-quadruplex and p53, probably further influencing the ferroptosis in cancer. G-quadruplex binds to ferric iron-related structures directly and may affect the p53 pathways as well as ferroptosis in cancer. In addition, G-quadruplex also interacts with p53 indirectly, including iron-sulfur cluster metabolism, telomere homeostasis, lipid peroxidation, and glycolysis. In this review, we summarized the latent interplay between G-quadruplex and p53 which focused mainly on ferroptosis in cancer to provide the potential understanding and encourage future studies.

Background Helicobacterpylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. Methods The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. Results GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746–179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo–YAP1 pathway in both in vitro and in vivo models. Conclusions Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.

Background: Platelets (PLT) have a significant effect in promoting cancer progression and hematogenous metastasis. However, the effect of platelet activation-related lncRNAs (PLT-related lncRNAs) in gastric cancer (GC) is still poorly understood. In this study, we screened and validated PLT-related lncRNAs as potential biomarkers for prognosis and immunotherapy in GC patients.Methods: We obtained relevant datasets from the Cancer Genome Atlas (TCGA) and Gene Ontology (GO) Resource Database. Pearson correlation analysis was used to identify PLT-related lncRNAs. By using the univariate, least absolute shrinkage and selection operator (LASSO) Cox regression analyses, we constructed the PLT-related lncRNAs model. Kaplan-Meier survival analysis, univariate, multivariate Cox regression analysis, and nomogram were used to verify the model. The Gene Set Enrichment Analysis (GSEA), drug screening, tumor immune microenvironment analysis, epithelial-mesenchymal transition (EMT), and DNA methylation regulators correlation analysis were performed in the high- and low-risk groups. Patients were regrouped based on the risk model, and candidate compounds and immunotherapeutic responses aimed at GC subgroups were also identified. The expression of seven PLT-related lncRNAs was validated in clinical medical samples using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: In this study, a risk prediction model was established using seven PLT-related lncRNAs -(AL355574.1, LINC01697, AC002401.4, AC129507.1, AL513123.1, LINC01094, and AL356417.2), whose expression were validated in GC patients. Kaplan-Meier survival analysis, the receiver operating characteristic (ROC) curve analysis, univariate, multivariate Cox regression analysis verified the accuracy of the model. We screened multiple targeted drugs for the high-risk patients. Patients in the high-risk group had a poorer prognosis since low infiltration of immune killer cells, activation of immunosuppressive pathways, and poor response to immunotherapy. In addition, we revealed a close relationship between risk scores and EMT and DNA methylation regulators. The nomogram based on risk score suggested a good ability to predict prognosis and high clinical benefits.Conclusion: Our findings provide new insights into how PLT-related lncRNAs biomarkers affect prognosis and immunotherapy. Also, these lncRNAs may become potential biomarkers and therapeutic targets for GC patients.