MiR-152 functioning as a tumor suppressor that interacts with DNMT1 in nasopharyngeal carcinoma.
Background
In recent years, miR-152 has been dysregulated in a variety of tumors and used as a tumor suppressor. Nevertheless, its role in nasopharyngeal carcinoma (NPC) remains unidentified.


Materials and methods
Real-time quantitative PCR (polymerase chain reaction) was performed to analyze the expression of miR-152 in NPC cell lines. MiR-152 expression profiles in NPC tissues were obtained from Gene Expression Omnibus (GEO GSE36682). The effect of miR-152 on the invasion and proliferation of NPC cells was determined through cell invasion, wound healing, and cell viability assays. Apoptosis was examined by flow cytometry, and Western blot was performed to measure expression of the target gene. Pyrosequencing was used to detect the methylation level of NPC cells.


Results
In this study, miR-152 was downregulated in the NPC tissues and cell lines. When miR-152 was enhanced, the invasion and migration of NPC cells were inhibited. However, miR-152 had no effect on the proliferation of NPC cells. Luciferase reporter gene analysis was performed, and the results showed that DNMT1 (DNA (cytosine-5)-methyltransferase 1) is a direct target of miR-152 in NPC cells. DNMT1 downregulation and miR-152 overexpression both reversed the effects of miR-152 inhibition on the NPC cells. In addition, miR-152 expression increased as a result of the inhibition of the methylation level of miR-152 when DNMT1 expression was downregulated.


Conclusion
The overexpression of miR-152 inhibited the migration and invasion of NPC cells by targeting DNMT1. Furthermore, DNMT1 regulated miR-152 expression through DNA methylation. Overall, the novel miR-152-DNMT1 regulatory circuit may provide better understanding of the pathogenesis of NPC and new epigenetic therapeutic target in NPC.
['Lu|Zhi-Wei|ZW|', 'Du|Ming-Yu|MY|', 'Qian|Lu-Xi|LX|', 'Zhang|Nan|N|', 'Gu|Jia-Jia|JJ|', 'Ding|Kai|K|', 'Wu|Jing|J|', 'Zhu|Hong-Ming|HM|', 'He|Xia|X|', 'Yin|Li|L|']
miR-152 DNMT1 NPC methylation