MiR-15a-5p Knockdown up-Regulated ABCB1 Expression and Abated HNSCC Progression via the NF-κB Signaling Pathway.

Abstract

Background: The high invasion and heterogeneity of head and neck squamous cell carcinoma (HNSCC) commonly leads to poor clinical outcomes. Identification of reliable biomarkers for HNSCC is imperative.

Methods: The targeted gene with the highest mutation was screened out in cBioPortal database, and the interactive microRNAs (miRNAs) were identified by miRNA-mRNA co-expression analysis. CCK-8 and transwell assays were used to explore the proliferative, migrative, and invasive behaviors of HNSCC cells. The dual-luciferase reporter assay and cell transfection experiment were conducted. The role of miR-15a-5p was investigated in the in vivo xenograft mouse model.

Results: ATP binding cassette transporter 1 (ABCB1) had the highest mutation frequency and multiple mutation types in HNSCC, and the decreased ABCB1 was significantly related to better prognosis of HNSCC patients. MiR-15a-5p was a regulator for ABCB1, which was up-regulated after miR-15a-5p inhibition in vitro. Furthermore, the miR-15a-5p knockdown significantly suppressed HNSCC cell proliferation, migration, and invasion in vitro, and reduced the HNSCC tumor growth and migration capabilities in vivo, possibly through NF-κB signaling pathway.

Conclusion: Collectively, miR-15a-5p knockdown increased the ABCB1 level and abated the HNSCC progression via the NF-κB signaling pathway. ABCB1 and miR-15a-5p were underlying predictors for HNSCC therapeutic biomarkers.