MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma

Abstract

Background MiRNAs can affect the radiosensitization of head and neck squamous cell carcinoma (HNSCC). We aimed to analyze the function of miR-125 family members in HNSCC using The Cancer Genome Atlas (TCGA) and determine their effect on radiation in laryngeal squamous cell cancer (LSCC). Methods First, we performed survival analysis for patients with laryngeal cancer, conducted pathway enrichment analysis, and predicted target genes. Then, we performed transfection, cell proliferation assays, reverse transcription polymerase chain reaction, apoptosis assays, micronucleus tests, and western blotting on hep-2 cells selected with puromycin. Results MiR-125 family members exhibited significantly different expression in HNSCC. MiR-125b-1-3p, miR-125b-2-5p, and miR-125b-5p expression was significantly associated with tumor–node–metastasis staging, clinical cancer stages, and early histological grades in HNSCC. Radiation therapy had a statistically significant effect on the expression of all miR-125 family members, except miR-125a-3p. Moreover, miR-125a-5p was related to overall survival in LSCC. Thus, we predicted 110 target genes and seven hub genes of miR-125a-5p. MiR-125a-5p expression was significantly improved after transfection, and the proliferation rate of cells transfected with lentivirus vector expressing miR-125a-5p was significantly reduced compared to that of parental and negative control group cells. The radiation effect was also enhanced in cells transfected with miR-125a-5p. The ratio of apoptotic cells transfected and exposed to X-rays (10 Gy) was distinctly higher than that of the Ad-control group. Micronucleus assay results in the Ad-miR-125a-5p group were significantly different from those in the parental and Ad-control groups. Western blotting analysis revealed that miR-125a-5p upregulated the apoptotic regulators P53 and rH2AX. Thus, miR-125a-5p may increase radiosensitivity in LSCC via upregulation of pro-apoptotic genes. Conclusions MiR-125 family members could be prognostic biomarkers of HNSCC, and miR-125a-5p may substantially improve HNSCC sensitivity to radiotherapy by activating P53. Upregulating miR-125a-5p via lentivirus vectors may be a novel strategy to strengthen the effect of radiotherapy on laryngeal cancer.

MiR-125 family improves the radiosensitivity of head and neck squamous cell carcinoma

“…The authors thank Huijun Li of Harbin Medical University for helpful advice. A preprint has previously been published [21]. However, I have recently made further revisions to the paper.…”