1. Medical Innovation Center, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College of Nanchang University, Nanchang, 330006, People's Republic of China.
2. Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, People's Republic of China.
3. Department of Orthopedics, the 908th Hospital of Joint Logistics Support Forces of Chinese PLA, Nanchang, 330006, People's Republic of China.
* Equal contribution and Co-first authors.
MYC proto-oncogene (MYC) is a transcription factor among the most commonly activated oncoproteins, playing vital roles in lipid metabolism and tumor aggressiveness with broad effects. However, it is still largely unknown about the regulating mechanisms of MYC in osteosarcoma (OS). In this study, we identify a circRNA with Reduced Expression in OS (termed as circREOS) generated from MYC gene, as a novel regulator of MYC and OS progression. CircREOS is down-regulated in OS cells and localized in the nucleus. CircREOS suppresses MYC expression, lipid metabolism and growth, invasion in OS cells. Mechanically, circREOS physically interacts with HuR (human antigen R) protein, and subsequently restrains its binding and activation on the 3'-UTR (untranslated region) of MYC mRNA, resulting in down-regulation of MYC and inhibition of OS. Moreover, circREOS serves as a tumor suppressor via targeting lipid metabolism. CircREOS reduces FASN expression and lipid accumulation through inhibiting MYC-facilitated FASN regulation. Taken together, these results indicate that circREOS suppress lipid synthesis and OS progression through inhibiting HuR-mediated MYC activation, providing a potential therapeutic target for OS.
Keywords: MYC, Osteosarcoma, circREOS, HuR, lipid metabolism