Published in:
Open Access 01-12-2024 | Sarcoma | Research
FAM83D acts as an oncogene by regulating cell cycle progression via multiple pathways in synovial sarcoma: a potential novel downstream target oncogene of anlotinib
Published in: Discover Oncology | Issue 1/2024
Login to get accessAbstract
Objective
Synovial Sarcoma (SS), a highly malignant mesenchymal neoplasm, typically carries a grim prognosis for patients presenting with high-grade or metastatic disease. Although Anlotinib, a new agent for treating soft tissue sarcomas, holds promise, its underlying mechanism remains incompletely understood. This investigation aims to delineate Anlotinib’s anticancer effectiveness and potential mechanistic underpinnings in patients suffering from advanced, refractory SS.
Materials and methods
Employing microarray assay, we examined the potential downstream targets of Anlotinib in SS therapy. A shRNA-based high-content screening was performed to identify candidate genes with the greatest influence on SW982 cell proliferation. The knockdown efficacy of selected genes within SW982 cells was confirmed using RT-qPCR as well as western blot analysis. To assess the effect of putative downstream elimination of genes with synovial sarcoma cells, cell proliferation, and apoptotic assays were carried out. Gene chip microarray as well as bioinformatics techniques were utilized to scrutinize potential signaling networks associated with the candidate downstream gene.
Results
QPCR verified high expression of FAM83D in SW982 cells, shRNA was designed to silence FAM83D by lentivirus transfection, apoptosis assay, and cell cycle arrest showing that FAM83D downregulation augments apoptosis in SW982 cells and arrests cell cycle progression in the S stage. Inhibition of FAM83D expression upregulated STAT1 while downregulated BIRC5, MCM2, and CDK1 genes in vitro.
Conclusions
This experimental study identified FAM83D as a critical regulator that contributes to the proliferation and progression of SS, suggesting that FAM83D-regulated signaling pathway may serve as a prospective target in SS management.