MicroRNA miR-146a is induced by HTLV-1 tax and increases the growth of HTLV-1-infected T-cells

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia (ATL), which is an aggressive and fatal CD4(+) T cell malignancy. MicroRNA (miRNA), a novel class of RNA that regulates gene expression, is involved in many cellular processes such as growth, development and apoptosis. It has recently been linked to several cancer phenotypes. However, aberrant miRNA expression and its pathologic significance in ATL are not well documented. Here, we investigated the role of miRNAs in HTLV-1-related leukemogenesis. The results showed that miR-146a was upregulated in HTLV-1-infected T-cell lines compared to uninfected T-cell lines. Tax-induced miR-146a expression in a NF-κB-dependent manner and inhibited the expression of gene harboring the target sequence of miR-146a on its 3'UTR. Inhibition of miR-146a function by anti-miRNA inhibitor reduced the proliferation of HTLV-1-infected T-cell lines but not that of uninfected T-cell lines. Moreover, overexpression of miR-146a enhanced the growth of an HTLV-1-infected T-cell line. Our findings suggest that miR-146a is a potentially suitable therapeutic target of ATL.