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

J Invest Surg. 2024 Dec;37(1):2434096. doi: 10.1080/08941939.2024.2434096. Epub 2024 Nov 28.

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.

Keywords: ABCB1; HNSCC; miR-15a-5p; prognosis; progression.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B* / genetics
  • ATP Binding Cassette Transporter, Subfamily B* / metabolism
  • Animals
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / metabolism
  • Head and Neck Neoplasms* / pathology
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • NF-kappa B* / metabolism
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Signal Transduction* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Up-Regulation*
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • ATP Binding Cassette Transporter, Subfamily B
  • ABCB1 protein, human
  • NF-kappa B
  • MIRN15 microRNA, human
  • Biomarkers, Tumor