Rhein suppresses osteosarcoma progression via modulating the miR-328-3p/TCF7L2/FABP4 axis

Rhein (RH), an anthraquinone compound extracted from the Chinese herb rhubarb, exerts antitumour effects on various cancers. However, the role and underlying molecular mechanisms of RH in osteosarcoma remain unknown. In this study, we observed that RH significantly inhibited osteosarcoma cell proliferation, migration, invasion and stemness in vitro while promoting death and curtailing tumourigenesis in vivo. Mechanistically, RH downregulated the expression of FABP4 in osteosarcoma cells. The induction of death by RH was augmented by FABP4 knockdown and diminished by FABP4 overexpression. Depletion of FABP4 suppressed osteosarcoma cell proliferation in vitro and in vivo. Then, we found that TCF7L2 was directly bound to the FABP4 promoter and facilitated its transcription. Downregulation of TCF7L2 inhibited FABP4 expression and enhanced the anticancer effects of RH in osteosarcoma. Additionally, our investigations revealed that RH significantly upregulated miR-328-3p expression, resulting in the downregulation of TCF7L2 protein levels in osteosarcoma cells. Our findings indicate that miR-328-3p/TCF7L2/FABP4 axis is vital for the anticancer effects of RH and may be a potential therapeutic agent for osteosarcoma treatment.