MicroRNA miR-146a and further oncogenesis-related cellular microRNAs are dysregulated in HTLV-1-transformed T lymphocytes

We report that several microRNAs – miRs 21, 24, 146a, 155 and 223 – are deregulated in HTLV-1-transformed cells. They are all upregulated except for miR-223, which is downregulated. Each of those microRNAs has ties to cancer. Their expression pattern forms a uniform phenotype among HTLV-transformed cells when compared to HTLV-negative control cells. In particular, miR-146a expression was found to be directly stimulated by Tax via NF-κB-mediated transactivation of its promoter; a single NF-κB site proximal to the transcription start point was necessary and sufficient for this to happen. An in silico analysis of potential target genes revealed candidates that might be coregulated by two or more of the aforementioned overexpressed microRNAs.These data demonstrate that cellular microRNAs are deregulated in HTLV-1-transformed T cells. In the case of miR-146a, this could be directly attributed to HTLV's oncoprotein Tax. Interference with cellular microRNAs may be crucial to maintaining persistence or may facilitate transformation of host cells.Human T-lymphotropic virus type 1 (HTLV-1) is a δ-retrovirus infecting primarily CD4+ T lymphocytes in vivo. Lifelong persistence ensues, which, after decades, can entail an aggressive neoplastic disease, adult T cell leukemia/lymphoma (ATLL). Another HTLV-1-associated disease presents as progressive neurodegeneration termed HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) [1-4]. HTLV's persistence manifests itself in T cell clones which remain detectable over many years even in non-leukemic infected individuals [5,6]. In the face of a continuous immune response this requires constant replenishment of infected cells. The virus achieves this through replication mainly in its provirus form, stimulation of cell division and, as a consequence, clonal amplification of infected cells.HTLV-1 encodes accessory and regulatory proteins. While the accessory ones, p12, p30, p13 [7,8] and HBZ [9], are important for infectivity a