Circ_LRP6 facilitates osteosarcoma progression via the miR-122-5p/miR-204-5p/HMGB1 axis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Circular RNA LRP6 (circ_LRP6) is implicated in various cancers.
• The specific role and mechanism of circ_LRP6 in osteosarcoma (OS) remain largely unelucidated.

Purpose of the Study:

• To investigate the function and underlying molecular mechanisms of circ_LRP6 in osteosarcoma development.
• To determine if circ_LRP6 acts as a potential diagnostic biomarker for osteosarcoma.

Main Methods:

• Quantitative real-time PCR (qRT-PCR) to measure expression levels of circ_LRP6, miR-122-5p, miR-204-5p, and HMGB1.
• Cell counting kit-8 (CCK-8) and Transwell assays to assess cell proliferation, migration, and invasion.
• Bioinformatics analysis and dual-luciferase reporter assays to confirm molecular interactions.
• In vivo studies using a subcutaneous tumor formation model in nude mice.

Main Results:

• Osteosarcoma tissues exhibited significantly higher expression of circ_LRP6 and HMGB1, and lower expression of miR-122-5p and miR-204-5p compared to normal tissues.
• Knockdown of circ_LRP6 markedly inhibited osteosarcoma cell proliferation, migration, and invasion in vitro and tumor growth in vivo.
• Bioinformatics and experimental validation confirmed circ_LRP6 targets miR-122-5p and miR-204-5p, which in turn target HMGB1.
• Restoration of miR-122-5p/miR-204-5p or HMGB1 partially reversed the effects of circ_LRP6 knockdown.

Conclusions:

• Circ_LRP6 promotes osteosarcoma progression through the miR-122-5p/miR-204-5p/HMGB1 signaling pathway.
• Circ_LRP6 serves as a potential molecular biomarker for osteosarcoma.