The immune system is critical in modulating cancer progression. Pseudogenes are a special type of long non-coding RNAs that regulate different tumorigenic processes. However, the potential roles of pseudogenes in tumor-immune interaction remain largely unclear. Here, we reported that pseudogene RP11-424C20.2 and its parental gene UHRF1 were frequently up-regulated and positively correlated in liver hepatocellular carcinoma (LIHC) and thymoma (THYM), but associated with distinct clinical outcomes. We further found that RP11-424C20.2 may act as a competing endogenous RNA (ceRNA) to increase UHRF1 expression through sponging miR-378a-3p. Functional enrichment analysis showed a strong association of UHRF1 with immune-related biological processes. We also observed that UHRF1 expression significantly correlated with immune infiltration, and different types of tumor-infiltrating immune cells displayed different impacts on clinical outcomes. Furthermore, UHRF1 expression in LIHC and THYM showed an opposite correlation with biomarkers from monocyte, dendritic cell, Th1 and T cell exhaustion. Mechanism investigations revealed that RP11-424C20.2/UHRF1 axis regulated immune escape of LIHC and THYM at least partly through IFN-γ-mediated CLTA-4 and PD-L1 pathway. These findings demonstrate a disparate role of RP11-424C20.2/UHRF1 axis in LIHC and THYM via regulating immune infiltrates, and also indicate a therapeutic value for UHRF1 inhibitors in combination with anti-PD-L1/CLTA-4 blockade.

Triple-negative breast cancer (TNBC) is the most aggressive molecular subtype of breast cancer. Curcumol, as a natural small molecule compound, has potential anti-breast cancer activity. In this study, we chemically synthesized a derivative of curcumol, named HCL-23, by structural modification and explored its effect on and underlying mechanism regarding TNBC progression. MTT and colony formation assays demonstrated that HCL-23 significantly inhibited TNBC cells proliferation. HCL-23 induced G2/M phase cell cycle arrest and repressed the capability of migration, invasion, and adhesion in MDA-MB-231 cells. RNA-seq results identified 990 differentially expressed genes including 366 upregulated and 624 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) revealed that these differentially expressed genes were obviously enriched in adhesion, cell migration, apoptosis, and ferroptosis. Furthermore, HCL-23 induced apoptosis via the loss of mitochondrial membrane potential and the activation of the caspase family in TNBC cells. In addition, HCL-23 was verified to trigger ferroptosis through increasing cellular reactive oxygen species (ROS), labile iron pool (LIP), and lipid peroxidation levels. Mechanistically, HCL-23 markedly upregulated the expression of heme oxygenase 1 (HO-1), and the knockdown of HO-1 could attenuate ferroptosis induced by HCL-23. In animal experiments, we found that HCL-23 inhibited tumor growth and weight. Consistently, the upregulation of Cleaved Caspase-3, Cleaved PARP, and HO-1 expression was also observed in tumor tissues treated with HCL-23. In summary, the above results suggest that HCL-23 can promote cell death through activating caspases-mediated apoptosis and HO-1-dependent ferroptosis in TNBC. Therefore, our findings provide a new potential agent against TNBC.

Aim: We aim to identify differentially expressed long noncoding RNAs (lncRNAs) and explored their functional roles in stomach adenocarcinoma. Materials & methods: Based on public omics data, we identified disregulated lncRNAs and investigated their prognostic values and potential functions based on ceRNA hypothesis. Results: Among the 52 differentially expressed lncRNAs, upregulated RP11-169F17.1 and RP11-669N7.2 were significantly associated with both poor overall survival and disease-free survival. RP11-169F17.1 and RP11-669N7.2 strongly correlated with microRNAs in cancer, cell proliferation and differentiation. RP11-169F17.1 and RP11-669N7.2 closely related to Helicobacter pylori infection-induced gastritis, duodenal ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Conclusion: RP11-169F17.1 and RP11-669N7.2 act as novel prognostic biomarkers of stomach adenocarcinoma and may also play an important role in H. pylori infection-induced gastric diseases.

In the theory of traditional Chinese medicine (TCM), "liver-qi" stagnation and heat-induced toxicity represent the main etiologies of breast cancer. Recently, several TCMs with heat-clearing and detoxification efficacy have shown inhibitory effects on breast cancer. Jin'gan capsules (JGCs), initially approved to treat colds in China, are a heat-clearing and detoxification TCM formula. However, the anticancer activity of JGCs against breast cancer and its underlying mechanisms remain unclear. First, we assessed the antiproliferative activity of JGCs in breast cancer cell lines and evaluated their effects on cell apoptosis and the cell cycle by flow cytometry. Furthermore, we identified the potential bioactive components of JGCs and their corresponding target genes and constructed a bioactive compound-target interaction network by ultra-performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-HR-MS/MS) and network pharmacology analysis. Finally, the underlying mechanism was investigated through gene function enrichment analysis and experimental validation. We found that JGCs significantly inhibited breast cancer cell growth with IC₅₀ values of 0.56 ± 0.03, 0.16 ± 0.03, and 0.94 ± 0.09 mg/mL for MDA-MB-231, MDA-MB-468, and MCF-7, respectively. In addition, JGC treatment dramatically induced apoptosis and S phase cell cycle arrest in breast cancer cells. Western blot analysis confirmed that JGCs could regulate the protein levels of apoptosis- and cell cycle-related genes. Utilizing UPLC-HR-MS/MS analysis and network pharmacology, we identified 7 potential bioactive ingredients in JGCs and 116 antibreast cancer targets. Functional enrichment analysis indicated that the antitumor effects of JGCs were strongly associated with apoptosis and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Western blot analysis validated that JGC treatment markedly decreased the expression levels of p-JAK2, p-STAT3, and STAT3. Our findings suggest that JGCs suppress breast cancer cell proliferation and induce cell cycle arrest and apoptosis partly by inhibiting the JAK2/STAT3 signaling pathway, highlighting JGCs as a potential therapeutic candidate against breast cancer.