Radiation induces submandibular gland damage by affecting Cdkn1a expression and regulating expression of miR-486a-3p in a xerostomia mouse model.

Abstract

Radiotherapy has been proven to be an effective treatment strategy for inhibiting head-and-neck cancer. However, side effects are common when using high-dosage irradiation, and the mechanism of action of this therapy has not been fully clarified. To discover targeting molecules involved in an electron radiation-induced xerostomia murine model. The xerostomia model mice were divided into Gy-3 (n = 5), Gy-7 (n = 5), and Gy-21 (n = 5) groups, and were compared to a negative control (NC) group. Drinking water amount, saliva volume, submandibular gland weight, and body weight were recorded. Real-time polymerase chain reaction (RT-PCR) was performed to amplify gene transcription. Hematoxylin and eosin (H&E) staining was used to identify submandibular gland damage. The dual-luciferase assay was used to observe the interaction between the Cdkn1a gene and miR-486a-3p. Electron radiation significantly increased the drinking water amount, and decreased saliva volume and body weight compared to mice without radiation treatment (p < 0.05). The H&E staining showed that electron radiation damaged the submandibular gland. Electron radiation also triggered significantly higher transcription of the Cdkn1a gene in the submandibular gland of xerostomia mice compared to those without radiation treatment (p < 0.05). The dual-luciferase assay demonstrated that miR-486a-3p interacted with the Cdkn1a gene (miRNA-mRNA). Radiation was found to induce damage of the submandibular gland and affect Cdkn1a expression by regulating the expression of miR-486a-3p in a xerostomia murine model. Therefore, modulation of miR-486a-3p and the Cdkn1a gene in a xerostomia murine model might improve damage of the submandibular gland.