miR-1343-3p, mediated by LncRNA ASMTL-AS1, induces ferroptosis in osteosarcoma progression by targeting TYRO3.

Abstract

Osteosarcoma (OS) is a highly aggressive bone malignancy that predominantly affects children and adolescents. Ferroptosis, a newly recognized form of programmed cell death characterized by iron-dependent lipid peroxidation, has emerged as a promising therapeutic target in OS. However, the regulatory mechanisms underlying ferroptosis in OS remain incompletely understood. In this study, we investigated the role of microRNA-1343-3p (miR-1343-3p) in OS ferroptosis. We found that inhibition of miR-1343-3p reduced ferroptosis and promoted OS cell proliferation in vitro and in vivo. Mechanistically, miR-1343-3p directly targeted the 3' untranslated region (3'UTR) of TYRO3, a member of the TAM receptor tyrosine kinase family. TYRO3 knockdown restored ferroptotic sensitivity suppressed by miR-1343-3p inhibition. Furthermore, the long non-coding RNA ASMTL-AS1 was identified as a competing endogenous RNA (ceRNA) for miR-1343-3p, thereby regulating TYRO3 expression. Collectively, our results reveal a novel ASMTL-AS1/miR-1343-3p/TYRO3 axis that modulates ferroptosis and OS progression, offering new insights into potential therapeutic targets for OS.