Abstract
Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes the aggressive and lethal malignancy of CD4+ T-lymphocytes called adult T-cell leukemia/lymphoma (ATLL). MicroRNAs (miRNAs), a class of short, noncoding RNAs, regulate gene expression by targeting mRNAs for translational repression or cleavage. miRNAs are involved in many aspects of cell biology linked with formation of several cancer phenotypes. However, the relation between miRNAs and pathologic implication in ATLL is not well elucidated. Here, we evaluated the roles of cellular miRNAs in ATLL caused by HTLV-1. We found that the expression of miR-155 was increased in HTLV-1-positive T-cell lines. miR-155 expression was enhanced by Tax and binding of transcription factors, NF-κB and AP-1, on the transcription binding sites of miR-155 gene promoter region is important to increase the expression of miR-155 by Tax. Transfection of anti-miR-155 inhibitor, which inhibits the function of miR-155, inhibited the growth of HTLV-1-positive T-cell lines. On the other hand, the growth of HTLV-1-negative T-cell lines was not changed by transfection of anti-miR-155. Forced expression of miR-155 enhanced the growth of HTLV-1-positive T-cell lines. These findings indicate that targeting the functions of miRNAs is a novel approach to the prevention or treatment of ATLL.
Highlights
Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes adult T-cell leukemia/lymphoma (ATLL), which is a unique malignancy of CD4+ T cells [1]
Our study demonstrated that miR-155 is highly expressed in HTLV-1-positive T-cell lines
Inhibition of miR-155 by anti-miR-155 inhibitor suppressed the growth of HTLV-1-positive T-cell lines
Summary
Human T-cell leukemia virus type 1 (HTLV-1) is the pathogen that causes adult T-cell leukemia/lymphoma (ATLL), which is a unique malignancy of CD4+ T cells [1]. HTLV1 transforms the infected CD4+ T lymphocytes and causes ATLL in 2–4% of infected individuals 50–60 years after infection [1, 2]. There are four subtypes of ATLL: acute, lymphoma, chronic, and smoldering types. The median survival time is more than 2 years in the relatively indolent chronic and smoldering types, the prognosis of ATLL in aggressive type, acute and lymphoma types, is very poor with a median survival time of less than 1 year [3]. At present, no curative therapy for ATLL has been established. Identification of good therapeutic targets and development of new therapeutic strategies for ATLL are urgent issues for public health in an endemic area
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