Pleckstrin homology-like domain family A member 2 (PHLDA2) displays low expression in human osteosarcoma as a proapoptosis factor. miRNAs have been shown to be important in modulating translation and therapeutic responsiveness in solid tumors.
Overall, our study demonstrates that TSSC3 inhibits the stem-like phenotype and Nanog expression by inactivation of the Src/Akt pathway; this emphasizes the importance of Nanog in osteosarcoma stem cells.
TSSC3 expression (P=0.032, HR=0.405, 95%CI=0.177-0.926) and metastasis (P=0.010, HR=2.849, 95%CI=1.291-6.287) were considered to be independent prognostic factors in osteosarcoma.
Taken together, these observations suggest that the epigenetic regulation of TSSC3, a pro-apoptosis gene, provides valuable insights into possible osteosarcoma therapies.
Furthermore, overexpression of TSSC3 was found to induce apoptosis of OS T-ICs through increasing cleaved caspase-3 (active form), increasing the release of Cyt c and decreasing pro-caspase-9 (pro-enzyme form), as well as disruption of the mitochondrial membrane potential (ΔΨ).