Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A.
Upregulation of MiR-155 in nasopharyngeal carcinoma is partly driven by LMP1 and LMP2A and downregulates a negative prognostic marker JMJD1A.
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鼻咽癌中 MiR-155 的上调部分由 LMP1 和 LMP2A 驱动，并下调阴性预后标志物 JMJD1A。
DOI：
10.1371/journal.pone.0019137
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发表时间：
2011-04-26
期刊：
影响因子：
3.7
通讯作者：
Ernberg I
中科院分区：
文献类型：
--
作者：
Du ZM;Hu LF;Wang HY;Yan LX;Zeng YX;Shao JY;Ernberg I
microRNA-155（miR-155）的作用与几种人类肿瘤的发生有关。然而，miR-155在鼻咽癌（NPC）中的表达模式尚未研究。本研究旨在探讨miR-155在鼻咽癌组织中的表达模式及其可能的功能，寻找miR-155的靶点，并评价其在鼻咽癌中的临床应用价值。实时荧光定量PCR和原位杂交检测发现miR-155在两种EB病毒（EBV）阴性的NPC来源的细胞系CNE 1和TW 03以及NPC临床样品中上调。EBV编码的LMP 1和LMP 2A可进一步增强miR-155在NPC CNE 1和TW 03细胞中的表达。在生物信息学筛选中，JMJD 1A和BACH 1被鉴定为miR-155的推定靶标。miR-155的过表达下调了与JMJD 1A和BACH 1的3′UTR融合的荧光素酶转录物。miR-155模拟物可下调JMJD 1A和BACH 1的表达，而miR-155抑制剂可上调JMJD 1A的表达。此外，JMJD 1A的下调与NPC患者的TNM分期（p = 0.023）、较低的5年生存率（p = 0.021）和较低的5年无病生存率（p = 0.049）显著相关。 综上所述，miR-155在NPC中的上调部分由LMP 1和LMP 2A驱动，并导致JMJD 1A的下调，这与NPC患者的N分期和不良预后相关。miR-155和JMJD 1A作为鼻咽癌治疗靶点的潜力有待进一步研究。
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.
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