KMID : 0613820170270020149
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Journal of Life Science 2017 Volume.27 No. 2 p.149 ~ p.154
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MicroRNA-23b is a Potential Tumor Suppressor in Diffuse Large B-cell Lymphoma
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Nam Je-Hyun
Kim Eun-Kyung Kim Jin-Young Jeong Da-Woom Kim Dong-Uk Kwak Bo-Mi Kim Sang-Woo
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Abstract
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Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-hodgkin lymphoma. Advances in the chemotherapeutic treatment of this disease have improved the outcomes of DLBCL; nonetheless, many patients still die of DLBCL, and therefore, a better understanding of this disease and identification of novel therapeutic targets are urgently required. In a recent gene expression profiling study, PDE (phosphodiesterase) 4B was found to be overexpressed in chemotherapy-resistant tumors. The major function of PDE4B is to inactivate the second messenger cyclic 3¡¯,5¡¯ monophosphate (cAMP) by catalyzing the hydrolysis of cAMP to 5¡¯AMP. It is known that cAMP induces cell cycle arrest and/or apoptosis in B cells, and PDE4B abolishes cAMP¡¯s effect on B cells. However, the mechanism by which PDE4B is overexpressed remains unclear. Here, we show that the aberrant expression of miRNA may be associated with the overexpression of this gene. The PDE4B 3¡¯ untranslated region (UTR) has three functional binding sites of miR-23b, as confirmed by luciferase reporter assays. Interestingly, miR-23b-binding sites were evolutionarily conserved from humans to lizards, implying the critical role of PDE4B-miR-23b interaction in cellular physiology. The ectopic expression of miR-2 3b repressed PDE4B mRNA levels and enhanced intracellular cAMP concentrations. Additionally, miR-23b expression inhibited cell proliferation and survival of DLBCL cells only in the presence of forskolin, an activator of adenylyl cyclase, suggesting that miR-23b¡¯s effect is via the downregulation of PDE4B. These results together suggest that miR-23b could be a therapeutic target for overcoming drug resistance by repressing PDE4B in DLBCL.
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KEYWORD
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cAMP, DLBCL, MicroRNA, miR-23b, PDE4B
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