Niu Man, Gao Dan, Wen Qiuyuan, Wei Pingpin, Pan Suming, Shuai Cijun, Ma Huiling, Xiang Juanjuan, Li Zheng, Fan Songqing, Li Guiyuan, Peng Shuping
Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China.
Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, 410078, China.
BMC Cancer. 2016 Mar 15;16:218. doi: 10.1186/s12885-016-2253-x.
Nasopharyngeal carcinoma (NPC) is prevalent in South East Asia and Southern China particularly, despite the reported 5-year survival ratio is relative higher than other deadly cancers such as liver, renal, pancreas cancer, the lethality is characterized by high metastatic potential in the early stage and high recurrence rate after radiation treatment. MicroRNA-29c was found to be down-regulated in the serum as well as in the tissue of nasopharyngeal carcinoma tissue.
In this study, we found accidentally that the transfection of pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a but doesn't affect that of miR-222 using real-time quantitative PCR in nasopharyngeal carcinoma cell lines. To explore the molecular mechanism of the regulatory role, the cells are treated with 5-Aza-2-deoxycytidine (5-Aza-CdR) treatment and the level of miR-34c and miR-449a but not miR-222 accumulated by the treatment. DNA methyltransferase 3a, 3b were down-regulated by the 5-Aza-CdR treatment with western blot and real-time quantitative PCR.
We found that pre-miR-29c or miR-29c mimics significantly increases the expression level of miR-34c and miR-449a. We further found DNA methyltransferase 3a and 3b are the target gene of miR-29c. Restoration of miR-29c in NPC cells down-regulated DNA methyltransferase 3a, 3b, but not DNA methyltransferase T1.
The regulation of miR-29c/DNMTs/miR-34c\449a is an important molecular axis of NPC development and targeting DNMTs or restoring of miR-29c might be a promising therapy strategy for the prevention of NPC.
鼻咽癌（NPC）在东南亚尤其是中国南方地区较为普遍。尽管报道显示其5年生存率相对高于肝癌、肾癌、胰腺癌等其他致命癌症，但其致死性表现为早期转移潜力高以及放疗后复发率高。研究发现，鼻咽癌组织的血清和组织中MicroRNA - 29c表达下调。
在本研究中，我们意外发现，在鼻咽癌细胞系中，转染pre - miR - 29c或miR - 29c模拟物可通过实时定量PCR显著提高miR - 34c和miR - 449a的表达水平，但不影响miR - 222的表达水平。为探究这种调控作用的分子机制，用5 - 氮杂 - 2'-脱氧胞苷（5 - Aza - CdR）处理细胞，处理后miR - 34c和miR - 449a的水平升高，而miR - 222不受影响。通过蛋白质免疫印迹法和实时定量PCR检测发现，5 - Aza - CdR处理使DNA甲基转移酶3a、3b表达下调。
我们发现pre - miR - 29c或miR - 29c模拟物可显著提高miR - 34c和miR - 449a的表达水平。我们进一步发现DNA甲基转移酶3a和3b是miR - 29c的靶基因。在NPC细胞中恢复miR - 29c可下调DNA甲基转移酶3a、3b，但不影响DNA甲基转移酶T1。
miR - 29c/DNMTs/miR - 34c\449a调控是NPC发生发展的重要分子轴，靶向DNMTs或恢复miR - 29c可能是预防NPC的一种有前景的治疗策略。
