Circular RNA circ-CHI3L1.2 modulates cisplatin resistance of osteosarcoma cells via the miR-340-5p/LPAATβ axis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Chemotherapy resistance significantly impacts osteosarcoma patient outcomes.
• Circular RNAs (circRNAs) are emerging as key regulators of drug resistance in various cancers.
• The specific role of circRNA chitinase 3-like 1.2 (CHI3L1.2) in osteosarcoma chemoresistance remains underexplored.

Purpose of the Study:

• To investigate the function and mechanism of circRNA CHI3L1.2 in cisplatin resistance in osteosarcoma.
• To elucidate the molecular pathways regulated by circ-CHI3L1.2 in chemoresistant osteosarcoma cells.

Main Methods:

• Quantification of circ-CHI3L1.2 expression in cisplatin-sensitive and resistant osteosarcoma cells.
• Functional assays including cell viability (IC50), apoptosis, migration, and invasion after circ-CHI3L1.2 knockdown.
• Analysis of key drug resistance markers (P-gp, MRP1, GSTP1) and epithelial-mesenchymal transition (EMT) markers.
• Investigation of the competitive endogenous RNA (ceRNA) network involving circ-CHI3L1.2, miR-340-5p, and LPAATβ.

Main Results:

• Circ-CHI3L1.2 expression was significantly higher in cisplatin-resistant osteosarcoma cells.
• Knockdown of circ-CHI3L1.2 reduced cisplatin IC50, decreased P-gp, MRP1, and GSTP1 expression, and promoted apoptosis.
• Circ-CHI3L1.2 knockdown induced mesenchymal-to-epithelial transition (MET), suppressing cell migration and invasion.
• Mechanistically, circ-CHI3L1.2 acts as a sponge for miR-340-5p, regulating LPAATβ expression.

Conclusions:

• Circ-CHI3L1.2 is upregulated in cisplatin-resistant osteosarcoma and contributes to chemoresistance.
• Circ-CHI3L1.2 knockdown resensitizes osteosarcoma cells to cisplatin via the miR-340-5p/LPAATβ axis.
• Circ-CHI3L1.2 represents a potential therapeutic target for overcoming cisplatin resistance in osteosarcoma.