CircREOS suppresses lipid synthesis and osteosarcoma progression through inhibiting HuR-mediated MYC activation

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• The MYC proto-oncogene is a key regulator of cell growth and lipid metabolism, frequently activated in various cancers.
• Understanding MYC regulation is crucial for developing effective osteosarcoma (OS) therapies.
• Mechanisms controlling MYC expression in OS remain incompletely understood.

Purpose of the Study:

• To identify novel regulators of MYC in osteosarcoma (OS).
• To investigate the role of a newly identified circRNA, circREOS, in OS progression and MYC regulation.
• To elucidate the molecular mechanisms underlying circREOS's tumor-suppressive function.

Main Methods:

• Identification and characterization of circREOS in OS cells.
• Assessment of circREOS expression levels in OS tissues and cell lines.
• Investigation of circREOS interaction with HuR protein and MYC mRNA.
• Analysis of circREOS's impact on MYC expression, lipid metabolism (including FASN), cell growth, and invasion in OS models.

Main Results:

• CircREOS, derived from the MYC gene, is significantly downregulated in OS.
• CircREOS suppresses MYC expression, cell proliferation, invasion, and lipid accumulation in OS.
• CircREOS physically binds to HuR, inhibiting its interaction with MYC mRNA's 3'-UTR.
• CircREOS reduces FASN expression, thereby decreasing lipid synthesis.

Conclusions:

• CircREOS acts as a tumor suppressor in osteosarcoma by inhibiting the HuR-mediated activation of MYC.
• CircREOS targets lipid synthesis pathways, including FASN regulation, to impede OS progression.
• CircREOS represents a promising therapeutic target for osteosarcoma treatment.