MicroRNA-140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Chemotherapy is a primary treatment for osteosarcoma, but chemoresistance, particularly multidrug resistance, limits its efficacy.
• Previous research identified genes involved in chemoresistance development, necessitating further investigation into regulatory mechanisms.

Purpose of the Study:

• To investigate the role of microRNA-140-5p (miR-140-5p) in osteosarcoma chemoresistance.
• To elucidate the molecular mechanisms underlying miR-140-5p's function in chemoresistance, including its targets and downstream pathways.

Main Methods:

• High-throughput microRNA expression analysis to identify miR-140-5p association with chemosensitivity.
• In vitro and in vivo experiments involving knockdown and overexpression of miR-140-5p in osteosarcoma cells.
• Luciferase assays and Western blot analysis to identify direct targets and signaling pathways, including HMGN5 and autophagy.

Main Results:

• Downregulation of miR-140-5p increased osteosarcoma cell resistance to multiple chemotherapeutics, while its overexpression sensitized cells to chemotherapy.
• HMGN5 was identified as a direct target of miR-140-5p, and it positively regulated autophagy.
• Silencing HMGN5 or inhibiting autophagy sensitized osteosarcoma cells to chemotherapy, indicating a miR-140-5p/HMGN5/autophagy regulatory loop.

Conclusions:

• miR-140-5p plays a crucial role in sensitizing osteosarcoma cells to chemotherapy by promoting autophagy via HMGN5.
• The miR-140-5p/HMGN5/autophagy pathway represents a potential therapeutic target for overcoming chemoresistance in osteosarcoma.
• miR-140-5p holds promise for improving chemoresistance prognosis and guiding treatment strategies in osteosarcoma patients.