circ_0002060 Enhances Doxorubicin Resistance in Osteosarcoma by Regulating the miR-198/ABCB1 Axis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Osteosarcoma (OS) is an aggressive bone cancer with significant challenges in chemotherapy due to drug resistance.
• Doxorubicin (DOX) is a key chemotherapeutic agent, but its efficacy is limited by acquired resistance in OS.
• Understanding the molecular mechanisms underlying DOX resistance is crucial for developing effective OS therapies.

Purpose of the Study:

• To investigate the role of circular RNA circ_0002060 in mediating doxorubicin resistance in osteosarcoma.
• To elucidate the underlying molecular mechanism involving circ_0002060, miR-198, and ABCB1 in DOX-resistant OS cells.
• To evaluate circ_0002060 as a potential therapeutic target and biomarker for osteosarcoma.

Main Methods:

• Quantitative real-time PCR and Western blot assays to measure expression levels of circ_0002060, miR-198, and ABCB1 in OS tissues and cells.
• Cell Counting Kit-8 (CCK-8) assay to determine IC50 values and assess DOX sensitivity.
• Colony formation assay, flow cytometry, and Western blot to evaluate cell proliferation, apoptosis, and related protein levels.
• Dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays to confirm molecular interactions.
• Xenograft assays to validate the effect of circ_0002060 on DOX resistance *in vivo*.

Main Results:

• circ_0002060 and ABCB1 were significantly upregulated, while miR-198 was downregulated in OS tissues and DOX-resistant OS cells.
• Silencing circ_0002060 reduced DOX resistance both *in vitro* and *in vivo*.
• circ_0002060 acts as a molecular sponge for miR-198, leading to the upregulation of ABCB1 and consequently enhancing DOX resistance.
• miR-198 directly binds to ABCB1, thereby decreasing DOX resistance.

Conclusions:

• circ_0002060 promotes doxorubicin resistance and osteosarcoma progression by regulating the miR-198/ABCB1 axis.
• circ_0002060 functions as a crucial mediator in the development of DOX resistance in osteosarcoma.
• circ_0002060 represents a promising therapeutic target and potential biomarker for improving osteosarcoma treatment outcomes.