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

This study explored the function and mechanisms of HOX transcript antisense RNA (HOTAIR) in the drug resistance of nasopharyngeal carcinoma (NPC). Quantitative PCR, Western blotting, MTT assay, flow cytometry, Transwell assay, and luciferase assay were performed. HOTAIR expression levels were upregulated in cisplatin (DDP)-resistant NPC tissues and cells. Knockdown of HOTAIR in DDP-resistant NPC cells increased cell sensitivity of DDP, as well as decreased cell viability, expression of chemoresistance-related proteins, migration and invasion, increased cell apoptosis. In addition, downregulation of microRNA 106a-5p (miR-106a-5p) expression and upregulation of SRY-box transcription factor 4 (SOX4) expression were observed in DDP-resistant NPC tissues and cells. MiR-106a-5p targets HOTAIR and SOX4; thus, silencing of HOTAIR significantly increased miR-106a-5p expression. The overexpression of miR-106a-5p significantly reversed the increase in SOX4 expression induced by HOTAIR lentivirus (Lv-HOTAIR). Knockdown of SOX4 reduced the drug resistance of DDP caused by the silencing of miR-106a-5p expression. In summary, HOTAIR enhanced DDP resistance in NPC cells by regulating the miR-106a-5p/SOX4 axis.

Automated summary

This study investigated the role of HOTAIR in drug resistance in nasopharyngeal carcinoma (NPC). It was found that upregulated expression of HOTAIR in NPC tissues and cells was associated with cisplatin resistance. Knockdown of HOTAIR increased cell sensitivity to cisplatin and reduced cell viability, chemoresistance-related protein expression, migration, invasion, and induced cell apoptosis. In addition, downregulation of miR-106a-5p expression and upregulation of SOX4 expression were observed in cisplatin-resistant NPC tissues and cells. HOTAIR regulated the miR-106a-5p/SOX4 axis to enhance drug resistance in NPC cells.