The effects of doxorubicin loaded aptamer S3-linked DNA tetrahedrons on nasopharyngeal carcinoma.

OBJECTIVE: Our research group in the early stage identified CD109 as the target of aptamer S3 in nasopharyngeal carcinoma (NPC). This study was to use S3 to connect DNA tetrahedron (DT) and load doxorubicin (Dox) onto DT to develop a targeted delivery system, and explore whether S3-DT-Dox can achieve targeted therapy for NPC. METHODS: Aptamer S3-conjugated DT was synthesized and loaded with Dox. The effects of S3-DT-Dox on NPC cells were investigated with laser confocal microscopy, flow cytometry, and MTS assays. A nude mouse tumor model was established from NPC 5-8F cells, and the in vivo anti-tumor activity of S3-DT-Dox was examined by using fluorescent probe labeling and hematoxylin-eosin staining. RESULTS: The synthesized S3-DT had high purity and stability. S3-DT specifically recognized 5-8F cells and NPC tissues in vitro. When the ratio of S3-DT to Dox was 1:20, S3-DT had the best Dox loading efficiency. The drug release rate reached the maximum (0.402 ± 0.029) at 48 h after S3-DT-Dox was prepared and mixed with PBS. S3-DT did not affect Dox toxicity to 5-8F cells, but reduced Dox toxicity to non-target cells. Meanwhile, S3-DT-Dox was able to specifically target the transplanted tumors and inhibit their growth in nude mice, with minor damage to normal tissues. CONCLUSION: Our study highlights the ability and safety of S3-DT-Dox to target NPC cells and inhibit the development NPC.

Classification related to immunogenic cell death predicts prognosis, immune microenvironment characteristics, and response to immunotherapy in lower-grade gliomas.

Background: Immunogenic cell death (ICD) is a form of cell death that elicits immune responses against the antigens found in dead or dying tumor cells. Growing evidence implies that ICD plays a significant role in triggering antitumor immunity. The prognosis for glioma remains poor despite many biomarkers being reported, and identifying ICD-related biomarkers is imminent for better-personalized management in patients with lower-grade glioma (LGG). Materials and methods: We identified ICD-related differentially expressed genes (DEGs) by comparing gene expression profiles obtained across Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) cohorts. On the foundation of ICD-related DEGs, two ICD-related clusters were identified through consensus clustering. Then, survival analysis, functional enrichment analysis, somatic mutation analysis, and immune characteristics analysis were performed in the two ICD-related subtypes. Additionally, we developed and validated a risk assessment signature for LGG patients. Finally, we selected one gene (EIF2AK3) from the above risk model for experimental validation. Results: 32 ICD-related DEGs were screened, dividing the LGG samples from the TCGA database into two distinct subtypes. The ICD-high subgroup showed worse overall survival (OS), greater immune infiltration, more active immune response process, and higher expression levels of HLA genes than the ICD-low subgroup. Additionally, nine ICD-related DEGs were identified to build the prognostic signature, which was highly correlated with the tumor-immune microenvironment and could unambiguously be taken as an independent prognostic factor and further verified in an external dataset. The experimental results indicated that EIF2AK3 expression was higher in tumors than paracancerous tissues, and high-expression EIF2AK3 was enriched in WHO III and IV gliomas by qPCR and IHC, and Knockdown of EIF2AK3 suppressed cell viability and mobility in glioma cells. Conclusion: We established novel ICD-related subtypes and risk signature for LGG, which may be beneficial to improving clinical outcome prediction and guiding individualized immunotherapy.

miR-33b in human cancer: Mechanistic and clinical perspectives.

The microRNAs (miRNAs), an extensive class of small noncoding RNAs (∼22 nucleotides), have been shown to have critical functions in various biological processes during development. miR-33b (or hsa-miR-33b) is down-regulated in cancer of multiple systems. Notably, at least 27 protein-coding genes can be targeted by miR-33b. miR-33b regulates the cell cycle, cell proliferation, various metabolism pathways, epithelial-mesenchymal transition (EMT), cancer cell invasion and migration, etc. In prostate cancer, Cullin 4B (CUL4B) can be recruited to the promoter to inhibit the expression of miR-33b. In gastric cancer, the hypermethylation of the CpG island regulated the expression of miR-33b. Besides, miR-33b could be negatively regulated by 7 competing-endogenous RNAs (ceRNAs), which are all long non-coding RNAs (lncRNAs). There are at least 4 signaling pathways, including NF-κB, MAP8, Notch1, and Wnt/ß-catenin signaling pathways, which could be regulated partially by miR-33b. Additionally, low expression of miR-33b was associated with clinicopathology and prognosis in cancer patients. In addition, the aberrant expression of miR-33b was connected with the resistance of cancer cells to 5 anticancer drugs (cisplatin, docetaxel, bortezomib, paclitaxel, and daunorubicin). Importantly, our work systematically summarizes the aberrant expression of miR-33b in various neoplastic diseases and the effect of its downregulation on the biological behavior of cancer cells. Furthermore, this review focuses on recent advances in understanding the molecular regulation mechanisms of miR-33b. Moreso, the relationship between the miR-33b expression levels and the clinicopathological data and prognosis of tumor patients was summarized for the first time. Overall, we suggest that the current studies of miR-33b are insufficient but provide potential hints and direction for future miR-33b-related research.