MicroRNA-646 inhibits proliferation and cell cycle progression of nasopharyngeal carcinoma cells by targeting mTOR

摘要

OBJECTIVE: To clarify whether microRNA-646 could regulate the proliferative potential and cell cycle progression of nasopharyngeal carcinoma cells through targeting mammalian target of rapamycin (mTOR). It, therefore, could influence the occurrence and progression of nasopharyngeal carcinoma. PATIENTS AND METHODS: Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to detect expression of the levels of microRNA-646 and mTOR in tumor tissues and paracancerous tissues of patients with nasopharyngeal carcinoma. Besides, their expressions in nasopharyngeal carcinoma cell lines were determined by qRT-PCR. Survival analysis was conducted to evaluate the sensitivity and specificity of microRNA-646 in diagnosing nasopharyngeal carcinoma. The overall survival of patients with nasopharyngeal carcinoma was calculated based on their expression levels of microRNA-646. The regulatory effects of microRNA-646 and mTOR on proliferative potential and cell cycle progression were explored by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Dual-luciferase reporter gene assay was conducted to verify the relationship between microRNA-646 and mTOR, which was further confirmed by Pearson correlation analysis. Finally, gain-of-function experiments were carried out to determine whether microRNA-646 could regulate the proliferative potential and cell cycle progression of nasopharyngeal carcinoma cells by targeting mTOR. RESULTS: MicroRNA-646 was lowly expressed in nasopharyngeal carcinoma tissues and cell lines. Survival analysis confirmed the diagnostic value of microRNA-646 in nasopharyngeal carcinoma. Besides, the nasopharyngeal carcinoma patients with high level of microRNA-646 were expected to have a longer 5-year survival time compared with those with low level. Overexpression of microRNA-646 inhibited the proliferative potential and cell cycle progression of HONE1 and SUNE1 nasopharyngeal carcinoma cells. Dual-luciferase reporter gene assay detected the binding of microRNA-646 to mTOR. Moreover, mTOR was highly expressed in nasopharyngeal carcinoma tissues and cell lines. A negative correlation was found between microRNA-646 and mTOR. That is, the overexpression of mTOR could reverse the inhibitory effects of microRNA-646 on the proliferative potential and cell cycle progression of HONE1 and SUNE1 cells. CONCLUSIONS: MicroRNA-646 remains a low level in nasopharyngeal carcinoma. It inhibits the proliferative potential and cell cycle progression of nasopharyngeal carcinoma cells by targeting mTOR. It can, therefore, inhibit the development of nasopharyngeal carcinoma.