State Key Laboratory of Oncology in South China, and Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
PLoS One. 2011 Apr 26;6(4):e19137. doi: 10.1371/journal.pone.0019137.
The role of microRNA-155 (miR-155) has been associated with oncogenesis of several human tumors. However the expression pattern of miR-155 has not been investigated in nasopharyngeal carcinoma (NPC). The present study was to assess miR-155 expression pattern and its possible function in NPC, to identify its targets and evaluate their clinical applications in NPC. MiR-155 was found to be upregulated in two Epstein-Barr virus (EBV) negative NPC derived cell lines CNE1 and TW03, as well as in NPC clinical samples by quantitative Real-time PCR and in situ hybridization detection. EBV encoded LMP1 and LMP2A could further enhance the expression of miR-155 in NPC CNE1 and TW03 cells. JMJD1A and BACH1 were identified as putative targets of miR-155 in a bioinformatics screen. Overexpression of miR-155 downregulated a luciferase transcript fused to the 3'UTR of JMJD1A and BACH1. MiR-155 mimic could downregulate the expression of JMJD1A and BACH1, while miR-155 inhibitor could upregulate JMJD1A expression in NPC cell lines. Moreover, downregulation of JMJD1A was significantly correlated with N stage in TNM classification (p = 0.023), a lower five-year survival rate (p = 0.021), and a lower five-year disease-free survival rate (p = 0.049) of NPC patients. Taken together, up-regulation of miR-155 in NPC is partly driven by LMP1 and LMP2A, and results in downregulation of JMJD1A, which is associated with N stage and poor prognosis of NPC patients. The potential of miR-155 and JMJD1A as therapeutic targets in NPC should be further investigated.
miR-155（微小 RNA-155）的作用与多种人类肿瘤的发生有关。然而，miR-155 在鼻咽癌（NPC）中的表达模式尚未得到研究。本研究旨在评估 miR-155 在 NPC 中的表达模式及其可能的功能，鉴定其靶标，并评估其在 NPC 中的临床应用。通过定量实时 PCR 和原位杂交检测发现，miR-155 在两种 EBV（Epstein-Barr virus）阴性 NPC 衍生细胞系 CNE1 和 TW03 以及 NPC 临床样本中上调。EBV 编码的 LMP1 和 LMP2A 可进一步增强 NPC CNE1 和 TW03 细胞中 miR-155 的表达。生物信息学筛选鉴定 JMJD1A 和 BACH1 为 miR-155 的潜在靶标。JMJD1A 和 BACH1 的 3'UTR 融合的荧光素酶转录本的过表达可下调 miR-155 的表达。miR-155 模拟物可下调 NPC 细胞系中 JMJD1A 和 BACH1 的表达，而 miR-155 抑制剂可上调 NPC 细胞系中 JMJD1A 的表达。此外，JMJD1A 的下调与 NPC 患者的 TNM 分期中的 N 期显著相关（p=0.023）、五年生存率较低（p=0.021）和无病生存率较低（p=0.049）。总之，NPC 中 miR-155 的上调部分由 LMP1 和 LMP2A 驱动，导致 JMJD1A 的下调，与 NPC 患者的 N 期和预后不良相关。miR-155 和 JMJD1A 作为 NPC 治疗靶点的潜力应进一步研究。
