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- Title
Epstein‑Barr virus‑encoded microRNA BART7 downregulates major histocompatibility complex class I chain‑related peptide A and reduces the cytotoxicity of natural killer cells to nasopharyngeal carcinoma.
- Authors
Wong, Thian-Sze; ChEN, Siqi; Zhang, Min-Juan; Chan, Jimmy Yu-Wai; Gao, Wei
- Abstract
Evasion from natural killer (NK) cell surveillance enables cancer to proliferate and spread at the early stages. NK cells mediate specific cytolysis by activation of the triggering receptors on their cell surface, of which the communication between natural killer group 2, member D (NKG2D) and major histocompatibility complex class I chain‑related peptide A (MICA) is a key regulatory axis. It has been indicated that cancer cells can reduce the surface expression of MICA, which thereby reduces the cytotoxicity of NK cells. In nasopharyngeal carcinoma (NPC), however, the underlying mechanism remains unclear. The present study indicated that MICA expression in NPC was regulated by TGFβ1. Furthermore, the human MICA gene was demonstrated to contain the c‑Myc binding site in the promoter region. Notably, the results suggested that TGFβ1 upregulated MICA expression by promoting c‑Myc expression. Additionally, the findings demosntrated that TGFβ1 expression in NPC was negatively controlled by Epstein‑Barr virus‑encoded microRNA BART7 (ebv‑miR‑BART7). In ebv‑miR‑BART7‑expressing NPC, the TGFβ1/c‑Myc/MICA regulatory axis was significantly inhibited. Notably, functional analysis indicated that NPC cells expressing ebv‑miR‑BART7 were less sensitive to the cytolysis mediated by NK cells. In conclusion, the present results revealed that ebv‑miR‑BART7‑expressing NPC may impair NK cells recognition and activity, which suggests that targeting ebv‑miR‑BART7 may be a useful therapeutic strategy in NPC immunotherapy.
- Subjects
NASOPHARYNX cancer; GENETICS of Epstein-Barr virus diseases; MICRORNA; DOWNREGULATION; MAJOR histocompatibility complex; KILLER cells
- Publication
Oncology Letters, 2018, Vol 16, Issue 3, p2887
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2018.9041