STAT6 phosphorylation upregulates microRNA-155 expression and subsequently enhances the pathogenesis of chronic lymphocytic leukemia.

Abstract

Chronic lymphocytic leukemia (CLL), a clonal expansion of CD5+ B cells, is the most common form of adult leukemia; however, the molecular mechanisms underlying its pathogenesis remain undetermined. It has been previously suggested that numerous biological factors, including cytokines, may be involved in the proliferation of malignant cells. For example, interleukin (IL)-4, IL-2, interferon-γ and tumor necrosis factor serve roles as inhibitors of cellular apoptosis; whereas IL-5 and IL-10 are inducers of cellular apoptosis. In the present study, the results demonstrated that the phosphorylation and activation of signal transducer and activator of transcription 6 (STAT6) was induced by IL-4 in a time-dependent manner. Notably, the expression level of microRNA (miR)-155 was increased in MEC-1 cells following treatment with IL-4; however, this effect was attenuated following STAT6 knockdown via RNA interference. In addition, STAT6 knockdown promoted cell apoptosis, which was partly attenuated by treatment with IL-4. Inhibition of miR-155 expression significantly increased cell apoptosis despite the presence of IL-4. The results of the present study suggested that treatment with IL-4 enhanced the expression of miR-155, which regulated CLL cell survival via the enhanced phosphorylation of STAT6.