Hederagenin (HED) has poor anticancer activity whose mechanism remains unclear and unsystematic. Free drugs for cancer treatment exhibit disadvantages such as poor targeting and efficacy. To address this problem, we constructed a nanoplatform of black phosphorus quantum dots (BPQDs) camouflaged with a platelet membrane (PLTm) carrying HED, termed PLT@BPQDs-HED. PLTm vesicles serve as a shell to encapsulate multiple high-efficiency drug-loaded nanocores, which can target tumor sites and significantly improve antitumor activity. Compared with free HED, this platform significantly reduced tumor cell viability and the mitochondrial membrane potential (MMP), while increasing the production of intracellular reactive oxygen species (ROS). The platform also significantly increased the amounts of terminal deoxyribonucleotide transferase mediated dUTP nick-end-labeling (TUNEL)-positive cells and decreased the number of Ki-67-positive cells. In addition, the platform upregulated proapoptotic factor Bax, downregulated the anti-apoptotic molecule Bcl-2, activated Caspase-9 and Caspase-3, and stimulated Cytochrome C release. Moreover, the platform promoted the formation of autophagosomes, upregulated Beclin-1, and promoted LC3-I conversion into LC3-II. This study demonstrated that the above platform significantly enhances tumor targeting and promotes mitochondria-mediated cell apoptosis and autophagy in tumor cells.

Lung adenocarcinoma (LUAD) is a highly heterogeneous malignancy, which makes prognosis prediction of LUAD very challenging. Ferroptosis is an iron-dependent cell death mechanism that is important in the survival of tumor cells. Long non-coding RNAs (lncRNAs) are considered to be key regulators of LUAD development and are involved in ferroptosis of tumor cells, and ferroptosis-related lncRNAs have gradually emerged as new targets for LUAD treatment and prognosis. It is essential to determine the prognostic value of ferroptosis-related lncRNAs in LUAD. In this study, we obtained RNA sequencing (RNA-seq) data and corresponding clinical information of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and ferroptosis-related lncRNAs by co-expression analysis. The best predictors associated with LUAD prognosis, including C5orf64, LINC01800, LINC00968, LINC01352, PGM5-AS1, LINC02097, DEPDC1-AS1, WWC2-AS2, SATB2-AS1, LINC00628, LINC01537, LMO7DN, were identified by Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis, and the LUAD risk prediction model was successfully constructed. Kaplan-Meier analysis, receiver operating characteristic (ROC) time curve analysis and univariate and multivariate Cox regression analysis and further demonstrated that the model has excellent robustness and predictive ability. Further, based on the risk prediction model, functional enrichment analysis revealed that 12 prognostic indicators involved a variety of cellular functions and signaling pathways, and the immune status was different in the high-risk and low-risk groups. In conclusion, a risk model of 12 ferroptosis related lncRNAs has important prognostic value for LUAD and may be ferroptosis-related therapeutic targets in the clinic.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and a leading cause of cancer-related deaths worldwide. Emerging studies have shown that circular RNAs (circRNAs) are differentially expressed in HCC and play an important role in HCC pathogenesis and metastasis. However, the mechanism of circRNA in the chemoresistance of HCC remains unclear. In this study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We identified a novel circRNA circRNA_101505 that was decreased in cisplatin-resistant HCC tissues and cell lines, and associated with a poor survival outcome. Gain-of-function investigations showed that overexpression of circRNA_101505 suppressed cancer cell growth in vivo and in vitro, and enhanced cisplatin toxicity in HCC cells. Mechanistic studies found that circRNA_101505 could sensitize HCC cells to cisplatin by sponging miR-103, and thereby promoting oxidored-nitro domain-containing protein 1 (NOR1) expression. In conclusion, the significant inhibitory effects indicate circRNA_101505 to be a potential therapeutic target for HCC treatment. Our findings provide significant evidence to further elucidate the therapeutic use of circRNA in HCC.

Objective: Early detection and treatment are particularly important to epithelial ovarian cancer (EOC). Studies have shown that circular RNA (circRNA) dysregulation is associated with the proliferation and metastasis of ovarian cancer cells. This study focused on the role of serum exosomal circular forkhead box protein P1 (circFoxp1) on survival outcome and cisplatin (DDP) resistance in patients with EOC. Methods: Quantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8, luciferase reporter assay, RNA immunoprecipitation, tumor xenograft in nude mice, and bioinformatic analysis were performed. Results: Circulating exosomal circFoxp1 was significantly increased in patients with EOC, especially in DDP-resistant EOC patients. circFoxp1 expression was positively associated with International Federation of Gynecology and Obstetrics stage, primary tumor size, lymphatic metastasis, distant metastasis, residual tumor diameter, and clinical response. Exosomal circFoxp1 also was an independent factor predicting survival and disease recurrence in patients with EOC. Overexpression of circFoxp1 could promote cell proliferation and confer DDP resistance, while knockdown of circFoxp1 could inhibit cell proliferation and enhance DDP sensitivity in vitro and in vivo. In addition, miR-22 and miR-150-3p mimic treatment attenuated circFoxp1-meadiated DDP resistance, while miR-22 and miR-150-3p inhibitor treatment enhanced DDP resistance that mitigated by circFoxp1 knockdown. Furthermore, circFoxp1 positively regulated the expression of CCAAT enhancer binding protein gamma (CEBPG) and formin like 3 (FMNL3) through miR-22 and miR-150-3p. Conclusions: circFoxp1 is an oncogene in EOC cells and can confer DDP resistance to EOC cells. Circulating exosomal circFoxp1 can be used as a biomarker and potential therapeutic target for EOC.