HOTAIR mediates cisplatin resistance in nasopharyngeal carcinoma by regulating miR-106a-5p/SOX4 axis

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• Nasopharyngeal carcinoma (NPC) exhibits resistance to cisplatin (DDP)-based chemotherapy.
• The role of HOX transcript antisense RNA (HOTAIR) in NPC drug resistance remains incompletely understood.

Purpose of the Study:

• To investigate the functional role and underlying mechanisms of HOTAIR in DDP resistance in NPC.
• To elucidate the regulatory relationship between HOTAIR, microRNA 106a-5p (miR-106a-5p), and SRY-box transcription factor 4 (SOX4) in NPC chemoresistance.

Main Methods:

• Quantitative PCR and Western blotting to assess gene and protein expression.
• MTT assay, flow cytometry, and Transwell assay to evaluate cell viability, apoptosis, migration, and invasion.
• Luciferase assay to confirm targeting interactions between molecules.

Main Results:

• HOTAIR expression was significantly upregulated in DDP-resistant NPC tissues and cells.
• HOTAIR knockdown resensitized NPC cells to DDP, reducing viability, chemoresistance markers, migration, invasion, and increasing apoptosis.
• HOTAIR regulated the miR-106a-5p/SOX4 axis, with HOTAIR targeting miR-106a-5p and influencing SOX4 expression.

Conclusions:

• HOTAIR enhances DDP resistance in NPC by modulating the miR-106a-5p/SOX4 signaling pathway.
• Targeting HOTAIR or the miR-106a-5p/SOX4 axis represents a potential therapeutic strategy for overcoming DDP resistance in NPC.