Epstein–Barr virus latent membrane protein 1 trans-activates miR-155 transcription through the NF-κB pathway

Abstract

The Epstein–Barr virus (EBV)-encoded latent membrane protein-1 (LMP1), a functional homologue of the tumor necrosis factor receptor family, substantially contributes to EBV's oncogenic potential by activating nuclear factor-κB (NF-κB). miR-155 is an oncogenic miRNA critical for B-cell maturation and immunoglobulin production in response to antigen. We report that miR-155 expression is much higher in EBV-immortalized B cells than in EBV-negative B cells. LMP1, but not LMP2, up-regulated the expression of miR-155, when transfected in EBV-negative B cells. We analyzed two putative NF-κB binding sites in the miR-155 promoter; both sites recruited NF-κB complex, in nuclear extract from EBV-immortalized cells. The exogenous expression of LMP1, in EBV-negative background, is temporally correlated to induction of p65 with binding on both NF-κB sites and with miR-155 overexpression. The induction of p65 binding together with increased RNA polymerase II binding, confirms that LMP1-mediated activation of miR-155 occurs transcriptionally. In reporter assays, miR-155 promoter lacking NF-κB binding sites was no longer activated by LMP1 expression and an intact AP1 site is needed to attain maximum activation. Finally, we demonstrate that LMP1-mediated activation of miR-155 in an EBV-negative background correlates with reduction of protein PU.1, which is a possible miR target.

An oncogenic role of miR-142-3p in human T-cell acute lymphoblastic leukemia (T-ALL) by targeting glucocorticoid receptor-α and cAMP/PKA pathways

“…As a pleiotropic transcription factor, nuclear factor-kB (NK-kB) is known to be constitutively activated in T-leukemic cells 41 and capable of regulating miRNAs, such as miR-155 and miR-146. 42,43 Coincidently, the NF-kB signaling pathway has been demonstrated to be involved GC resistance. 44,45 These facts cause us to speculate the regulation of miR-142-3p by NF-kB.…”

miRNA-based mechanism for the commitment of multipotent progenitors to a single cellular fate

“…4), another key transcription factor in osteoclast development that was shown to synergize with MITF (35). Repression of PU.1 by miR-155 is well-documented (18,33,36,37); yet because MITF expression alone is sufficient to reverse miR-155 activity, it likely constitutes the dominant player in this particular system.…”

Pivotal role of Interleukin-10 on microRNA-155 expression in regulation of the monocyte response in hypothermia.

“…In summary, we demonstrate here that miRNA-155 is instrumental in the (149,193,194,196). As Figure 15 indicates, there is no difference in miRNA-155 induction between 32°C and 39°C in the first 12h.…”

“…MicroRNAs are also transcribed like cytokine genes from DNA to RNA and also depend upon the activation of transcription factors. MiRNA-155 expression is induced by NF-KB (149,193). Furthermore, the MAPK-pathway has also been implicated in the induction of miRNA-155 (194)(195)(196).…”