Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Zhuhai Hospital of Jinan University, Zhuhai, China.
Mol Carcinog. 2018 Dec;57(12):1763-1779. doi: 10.1002/mc.22895. Epub 2018 Sep 19.
Nasopharyngeal carcinoma (NPC) has a high metastatic clinicopathological feature. As a carcinogen factor, N,N'-dinitrosopiperazine (DNP) is involved in NPC metastasis, but its precise mechanism has not been fully elucidated. Herein, we showed that DNP promotes NPC metastasis through upregulating miR-149. DNP was found to decrease Plakophilin3 (PKP3) expression, further DNP-decreased PKP3 was verified to be through upregulating miR-149. We also found that DNP induced proliferation, adhesion, migration and invasion of NPC cell, which was inhibited by miR-149-inhibitor. DNP may promote NPC metastasis through miR-149-decreased PKP3 expression. Therefore, DNP-increased miR-149 expression may be an important factor of NPC high metastasis, and miR-149 may serve as a molecular target for anti-metastasis therapy of NPC.
鼻咽癌（NPC）具有较高的转移性临床病理特征。N,N'-二亚硝基哌嗪（DNP）作为一种致癌因素，参与 NPC 的转移，但具体机制尚未完全阐明。本研究表明，DNP 通过上调 miR-149 促进 NPC 转移。研究发现 DNP 降低了桥粒斑蛋白 3（PKP3）的表达，进一步证实 DNP 降低 PKP3 是通过上调 miR-149 实现的。我们还发现，DNP 诱导 NPC 细胞的增殖、黏附、迁移和侵袭，而 miR-149 抑制剂则抑制了这一过程。DNP 可能通过降低 PKP3 的表达促进 NPC 转移。因此，DNP 上调 miR-149 的表达可能是 NPC 高转移的一个重要因素，miR-149 可能成为 NPC 抗转移治疗的一个分子靶点。
