Long Non-Coding RNA OIP5-AS1 Knockdown Enhances CDDP Sensitivity in Osteosarcoma via miR-377-3p/FOSL2 Axis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Drug resistance poses a significant challenge in cancer treatment.
• Long non-coding RNA OIP5-AS1 (Opa-interacting protein 5-antisense RNA 1) is implicated in acquired resistance.
• This study investigates the role of OIP5-AS1 in cisplatin resistance in osteosarcoma.

Purpose of the Study:

• To elucidate the mechanism by which OIP5-AS1 influences cisplatin resistance in osteosarcoma (OS).
• To determine the regulatory relationship between OIP5-AS1, miR-377-3p, and FOSL2 in OS drug resistance.

Main Methods:

• Quantitative real-time PCR for gene expression analysis (OIP5-AS1, miR-377-3p, FOSL2).
• Cell Counting Kit-8 and flow cytometry for assessing cell viability, IC50, and apoptosis.
• Western blot for protein expression analysis (MRP1, P-glycoprotein, BCL2, BAX, cleaved-caspase-3, FOSL2).
• Dual-luciferase reporter and RNA immunoprecipitation assays to confirm molecular interactions.
• In vivo xenograft tumor models to evaluate OIP5-AS1 function.

Main Results:

• OIP5-AS1 and FOSL2 were upregulated, while miR-377-3p was downregulated in cisplatin-resistant OS.
• OIP5-AS1 silencing reduced cell viability, increased apoptosis, and enhanced cisplatin sensitivity in OS cells.
• OIP5-AS1 acts as a molecular sponge for miR-377-3p, and FOSL2 is a target of miR-377-3p.
• In vivo, OIP5-AS1 knockdown suppressed tumor growth and improved cisplatin efficacy.

Conclusions:

• OIP5-AS1 promotes cisplatin resistance in osteosarcoma by sponging miR-377-3p.
• This mechanism leads to the upregulation of FOSL2, consequently decreasing cisplatin sensitivity.
• Targeting OIP5-AS1 may represent a therapeutic strategy to overcome drug resistance in osteosarcoma.