Recent Progress in the Methodologies to Identify Physiological Ligands of Siglecs

Siglecs, a family of receptor-like lectins, recognize glycoproteins and/or glycolipids containing sialic acid in the extracellular space and transduce intracellular signaling. Recently, researchers uncovered significant contributions of Siglecs in cancer immunity, renewing interest in this family of proteins. Previous extensive studies have defined how Siglecs recognize glycan epitopes (glycotopes). Nevertheless, the biological role of these glycotopes has not been fully evaluated. Recent studies using live cells have begun unraveling the constituents of Siglec ligands. These studies demonstrated that glycoprotein scaffolds (counter-receptors) displaying glycotopes are sometimes just as important as the glycotope itself. These new insights may guide future efforts to develop therapeutic agents to target the Siglec – ligand axis.

Splice-Variant Knock-Out of TGFβ Receptors Perturbates the Proteome of Ovarian Carcinoma Cells

The aim of this study was to analyze the biological role of different transforming growth factor-β (TGFβ) receptor splice variants in ovarian carcinoma (OC). Specific receptor variant knockouts (KO) were prepared using the CRISPR/Cas9 genome editing system in two OC cell lines, TβRI variant 1 (TβRIv1) KO in ES-2 cells and TβRII variant 1 (TβRIIv1) KO in OVCAR-8 cells. Control and KO cells were compared by proteomic analysis, functional tests, analysis of epithelial–mesenchymal transition (EMT) drivers, and Western blot of signaling proteins. Proteomic analysis revealed significant changes in protein pathways in the KO cells. TβRIv1 KO resulted in a significant reduction in both cellular motility and invasion, while TβRIIv1 KO significantly reduced cellular motility and increased Reactive Oxygen Species (ROS) production. Both receptor variant KOs reduced MET protein levels. Of the EMT drivers, a significant decrease in TWIST protein expression, and increase in SNAIL protein and MALAT1 mRNA levels were observed in the TβRIIv1 KO compared to control. A significant decrease in JNK1 and JNK2 activation was found in the TβRIv1 KO compared to control cells. These findings provide new insight regarding the biological role of the TGFβ receptor variants in the biology and potentially the progression of OC.

Circ-DONSON Knockdown Inhibits Cell Proliferation and Radioresistance of Breast Cancer Cells via Regulating SOX4

Background. Circular RNAs have been validated as critical regulators in the development of breast cancer (BC). Circ-DONSON is involved in the progression of glioma and gastric cancer. However, the biological role of circ-DONSON in BC remains unclear, and the aim of this study was to explore the biological role of circ-DONSON in BC. Methods. Human tissue samples and BC cell lines were collected in this study. siRNAs against circ-DONSON were transfected into BC cell lines for silencing of circ-DONSON. Quantitative real-time PCR was used to test the circ-DONSON expression. Cell counting kit-8 (CCK-8), 5-bromo-2′ deoxyuridine enzyme-linked immunosorbent assay (BrdU-ELISA), colony formation, and caspase-3 activity assays were used to assess cell proliferation, cell survival, and cell viability. Western blotting analysis was used to detect the protein expression levels. Results. Our findings showed that circ-DONSON showed high expression in BC tissues and cell lines. CCK-8 and BrdU-ELISA assays showed that circ-DONSON knockdown inhibited BC cell proliferation. Moreover, cell survival, cell viability, and caspase-3 activity assays showed that circ-DONSON knockdown reduced the radioresistance of BC cells. Mechanistically, circ-DONSON regulated BC cell proliferation and radioresistance via SRY-box transcription factor 4 (SOX4). SOX4 overexpression significantly rescued the effect of circ-DONSON knockdown on BC cell proliferation and radioresistance. Moreover, circ-DONSON activated the Wnt/β-catenin pathway in BC cells via SOX4. Conclusion. Our study concluded that circ-DONSON knockdown hindered cell proliferation and radioresistance through the SOX4/Wnt/β-catenin pathway in BC.