HMTH1 induces the metastasis and recurrence of the parotid adenoma by repairing DNA damage.

Objective: To investigate the effect of hMTH1 (human mutT homologue 1) on inducing the metastasis and recurrence of parotid adenoma, which may provide a new therapeutic direction for the prevention and treatment of parotid adenoma.

Patients And Methods: 30 cases of paraffin-embedded specimens of parotid adenoid cystic carcinoma (ACC) tissues and fresh parotid glands surgically resected in our hospital were collected as experimental group. 30 cases of surgically resected pleomorphic adenoma (PA) in the same period were selected as another experimental group. Meanwhile, 30 cases of normal parotid gland tissues (N) were collected as control group. The mRNA and protein expressions of hMTH1 in parotid gland tissues of patients with parotid adenoma before and after surgery were detected by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western blotting, respectively. HMTH1 expression levels in parotid gland tissues were also detected by immunohistochemistry. Proliferation, apoptosis and DNA damage of ACC-M cells treated with S-Crizotinib were detected by cell counting kit-8 (CCK-8) assay, flow cytometry and single cell gel electrophoresis, respectively.

Results: Both mRNA and protein expressions of hMTH1 in experimental group were significantly higher than those of control group. Moreover, a higher expression of hMTH1 was observed in ACC than that of PA, indicating that hMTH1 expression was positively correlated with the malignant degree of parotid adenoma. Furthermore, postoperative hMTH1 expression levels in patients with parotid adenoma were significantly lower than those before treatment, which were remarkably increased in recurrent patients. In vitro experiments demonstrated that S-Crizotinib, the hMTH1 inhibitor, could inhibit proliferation and induce apoptosis and DNA damage of ACC-M cells.

Conclusions: HMTH1 was upregulated in patients with parotid adenoma and recurrent patients after surgery. Meanwhile, S-Crizotinib induced DNA damage in ACC-M cells, indicating that hMTH1 induced the metastasis and recurrence of parotid adenoma by repairing DNA damage, providing a new strategy for the prevention and treatment of parotid adenoma.