MicroRNA-765 sensitizes osteosarcoma cells to cisplatin via downregulating APE1 expression

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Osteosarcoma (OS) is a prevalent bone cancer in children and adolescents.
• Elevated APE1 expression in OS correlates with reduced platinum sensitivity and poorer prognosis.
• The mechanisms driving high APE1 expression in OS remain unclear.

Purpose of the Study:

• To investigate the regulatory role of microRNAs (miRNAs) in APE1 expression within OS.
• To determine the impact of miR-765 on cisplatin sensitivity and DNA repair in OS.
• To assess the clinical significance of miR-765 and APE1 as prognostic markers in OS patients.

Main Methods:

• Bioinformatics analysis of APE1 3'-UTR to identify potential miRNA targets.
• Luciferase assays and Western blot to confirm miR-765 binding and APE1 downregulation.
• In vitro studies in OS cell lines and in vivo xenograft models to evaluate cisplatin sensitivity.
• Clinical data analysis of miR-765 and APE1 expression in OS patients (n=43) using Kaplan-Meier and Cox regression.

Main Results:

• miR-765 was identified as a direct regulator of APE1, downregulating its expression in OS cells.
• miR-765 enhanced OS cell sensitivity to cisplatin and reduced DNA repair activity.
• In vivo studies showed increased cisplatin sensitivity in OS xenografts treated with miR-765 agomir.
• Clinical data revealed a negative correlation between miR-765 and APE1 expression (p=0.045).
• High miR-765 expression was associated with significantly longer patient survival (22.0 vs. 9.0 months, p=0.001) and identified as an independent prognostic factor (p=0.007).

Conclusions:

• miR-765 sensitizes osteosarcoma cells to cisplatin by downregulating APE1 and impairing DNA damage repair.
• Elevated miR-765 expression is linked to improved survival in osteosarcoma patients.
• miR-765 represents a potential therapeutic target for overcoming cisplatin resistance in OS.