Induction of lytic Epstein-Barr virus infection in nasal NK/T-cell lymphoma

2014 Fiscal Year Final Research Report

• Project/Area Number: 25893008
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: Asahikawa Medical College
• Principal Investigator: UEDA Seigo 旭川医科大学, 医学部, 助教 (90447102)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Keywords: 鼻性NK/T細胞リンパ腫 / Epstein-Barr virus / BIRC5 / CDK1 / LMP1

Outline of Final Research Achievements

Nasal NK/T-cell lymphoma (NNKTL) is EBV-related malignancy and has a poor prognosis. An improved understanding of the mechanisms of NNKTL is crucial for identifying new targets of effective treatment modalities for this deadly disease. We found that inhibitors of Sp1 transcription factor dose-dependently decreased cell proliferation of NNKTL cells. This was associated with decrease in BIRC5 and CDK1 expressions and induction of apoptosis and cell-cycle arrest at G2/M phase in NNKTL cells. Knockdown of EBV-encoded LMP1 induced downregulation of CDK1 and BIRC5 expressions and apoptosis in NNKTL cells. Immunohistochemistry detected BIRC5 expression in LMP1-positive lymphoma cells of NNKTL biopsy specimens. Our results suggest that LMP1 upregulates CDK1 and BIRC5 expression, and these upregulations are essential for NNKTL growth. Thus, targeting CDK1 and BIRC5 by using Sp1 inhibitors might be an effective approach to treat NNKTL that is hallmarked by poor prognosis.

Free Research Field

医歯薬学