Analysis of SIGLEC12 expression, immunomodulation and prognostic value in renal cancer using multiomic databases.

Siglecs belong to a family of immune regulatory receptors predominantly found on hematopoietic cells. They interact with Sia, resulting in the activation or inhibition of the immune response. Previous reports have suggested that the SIGLEC12 gene, which encodes the Siglec-XII protein, is expressed in the epithelial tissues and upregulated in carcinomas. However, studies deciphering the role of Siglec-XII in renal cancer (RC) are still unavailable, and here we provide insights on this question. We conducted expression analysis using the Human Protein Atlas and UALCAN databases. The impact of SIGLEC12 on RC prognosis was determined using the KM plotter, and an assessment of immune infiltration with SIGLEC12 was performed using the TIMER database. GSEA was conducted to identify the pathways affected by SIGLEC12. Finally, using GeneMania, we identified Siglec-XII interacting proteins. Our findings indicated that macrophages express SIGLEC12 in the kidney. Furthermore, we hypothesize that Siglec-XII expression might be involved in the increase of primary RC, but this effect may not be dependent on the age of the patient. In the tumour microenvironment, oncogenic pathways appeared to be upregulated by SIGLEC12. Similarly, our analysis suggested that SIGLEC12-related kidney renal papillary cell carcinomas may be more suitable for targeted immunotherapy, such as CTLA-4 and PD-1/PD-L1 inhibitors. These preliminary results suggested that high expression of SIGLEC12 is associated with poor prognosis for RC. Future studies to assess its clinical utility are necessitated.

MicroRNA-Dependent Mechanisms Underlying the Function of a ß-Amino Carbonyl Compound in Glioblastoma Cells.

Glioblastoma (GB) is an aggressive brain malignancy characterized by its invasive nature. Current treatment has limited effectiveness, resulting in poor patients' prognoses. ß-Amino carbonyl (ß-AC) compounds have gained attention due to their potential anticancerous properties. In vitro assays were performed to evaluate the effects of an in-house synthesized ß-AC compound, named SHG-8, upon GB cells. Small RNA sequencing (sRNA-seq) and biocomputational analyses investigated the effects of SHG-8 upon the miRNome and its bioavailability within the human body. SHG-8 exhibited significant cytotoxicity and inhibition of cell migration and proliferation in U87MG and U251MG GB cells. GB cells treated with the compound released significant amounts of reactive oxygen species (ROS). Annexin V and acridine orange/ethidium bromide staining also demonstrated that the compound led to apoptosis. sRNA-seq revealed a shift in microRNA (miRNA) expression profiles upon SHG-8 treatment and significant upregulation of miR-3648 and downregulation of miR-7973. Real-time polymerase chain reaction (RT-qPCR) demonstrated a significant downregulation of CORO1C, an oncogene and a player in the Wnt/ß-catenin pathway. In silico analysis indicated SHG-8's potential to cross the blood-brain barrier. We concluded that SHG-8's inhibitory effects on GB cells may involve the deregulation of various miRNAs and the inhibition of CORO1C.

In Silico and In Vitro Mapping of Receptor-Type Protein Tyrosine Phosphatase Receptor Type D in Health and Disease: Implications for Asprosin Signalling in Endometrial Cancer and Neuroblastoma.

BACKGROUND: Protein Tyrosine Phosphatase Receptor Type D (PTPRD) is involved in the regulation of cell growth, differentiation, and oncogenic transformation, as well as in brain development. PTPRD also mediates the effects of asprosin, which is a glucogenic hormone/adipokine derived following the cleavage of the C-terminal of fibrillin 1. Since the asprosin circulating levels are elevated in certain cancers, research is now focused on the potential role of this adipokine and its receptors in cancer. As such, in this study, we investigated the expression of PTPRD in endometrial cancer (EC) and the placenta, as well as in glioblastoma (GBM). METHODS: An array of in silico tools, in vitro models, tissue microarrays (TMAs), and liquid biopsies were employed to determine the gene and protein expression of PTPRD in healthy tissues/organs and in patients with EC and GBM. RESULTS: PTPRD exhibits high expression in the occipital lobe, parietal lobe, globus pallidus, ventral thalamus, and white matter, whereas in the human placenta, it is primarily localised around the tertiary villi. PTPRD is significantly upregulated at the mRNA and protein levels in patients with EC and GBM compared to healthy controls. In patients with EC, PTPRD is significantly downregulated with obesity, whilst it is also expressed in the peripheral leukocytes. The EC TMAs revealed abundant PTPRD expression in both low- and high-grade tumours. Asprosin treatment upregulated the expression of PTPRD only in syncytialised placental cells. CONCLUSIONS: Our data indicate that PTPRD may have potential as a biomarker for malignancies such as EC and GBM, further implicating asprosin as a potential metabolic regulator in these cancers. Future studies are needed to explore the potential molecular mechanisms/signalling pathways that link PTPRD and asprosin in cancer.