Abstract
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.
Highlights
Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in certain areas of South-China, Southeast-Asia and North Africa [1]
MiR-155 is upregulated in NPC In situ hybridization was performed to evaluate miR-155 expression in NPC tumor cells and normal nasopharyngeal epithelium
Strong expression of miR-155 was observed in NPC tumor cells, while weak expression was observed in normal adjacent nasopharyngeal epithelium (Fig. 1A)
Summary
Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in certain areas of South-China, Southeast-Asia and North Africa [1]. NPC has a dominant clinicopathological behavior of loco-regional recurrence and metastasis, which differs from other types of head and neck cancers [4]. NPC tumors are sensitive to radiotherapy and chemotherapy, treatment failure is high due to regional lymph node metastasis, distant metastasis and local recurrence [5]. MicroRNAs exert their gene regulatory activity primarily by imperfect base pairing to the 39 UTR of their target mRNAs, leading to mRNA degradation or translational inhibition. They are involved in numerous cellular processes including proliferation, differentiation, apoptosis and metabolism [6]
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