Abstract
BACKGROUND: Collagen triple helix repeat containing 1 (CTHRC1) is an oncogene in numerous human cancers including oral squamous cell carcinoma (OSCC). However, whether and how CTHRC1 influences OSCC progression through ferroptosis has not been completely clarified. METHODS: qRT-PCR were conducted to assess CTHRC1 expression in OSCC. The proliferation of OSCC cells were assessed through 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation, and CCK-8 assays. Flow cytometry was used to analyze the apoptotic cells of OSCC cells. Ferroptosis was assessed based on the amounts of MDA, lipid ROS, intracellular Fe(2+), and ferroptosis-related proteins. TGF-β/Smad pathway-related protein were detected by Western blot. RESULTS: Pronounced overexpression of CTHRC1 was observed in OSCC cell lines (SCC-9, CAL-27 and SCC-25). Knockdown CTHRC1 overtly inhibited cell proliferation but induced apoptosis in OSCC cells. Moreover, silencing of CTHRC1 could stimulate ferroptosis, as well as inhibit the activation of TGF-β/Smad pathway. Treatment with SRI-011381, a TGF-β/Smad pathway specific agonist, significantly reversed the promoting effect of CTHRC1 silencing on ferroptosis in OSCC cells. CONCLUSIONS: Our findings indicate that knockdown of CTHRC1 stimulates ferroptosis in OSCC through inhibiting TGF-β/Smad pathway, which provides important experimental data and theoretical basis for the management, diagnosis, and treatment of OSCC.