Central nervous system lymphoma (CNSL) remains a diagnostical and therapeutical challenge. MiRNAs post-transcriptionally regulate expression of targeted mRNAs through binding to their 3' UTR to inhibit their translation or promote their degradation. Oncoprotein inhibitory member of the ASPP family (iASPP), a key inhibitor of tumor suppressor p53, has been reported to play oncogenic role in cancers. Our present study was aimed to determine whether the miR-184/iASPP axis is involved in the proliferation and invasion of CNSL. A reduced level of miR-184 was observed in CNSL tissues. Exogenous miR-184 inhibited cell survival and invasion, as well as the tumor volumes, while miR-184 inhibition could reverse this process. The RNA and protein levels of iASPP were significantly inhibited by miR-184, and the 3' UTR of iASPP was shown to be a target of miR-184. The expression of iASPP was up-regulated in CNSL tissues, compared to that of the normal brain tissues. The inhibition of iASPP by shRNA iASPP significantly repressed CNSL cells' proliferation and invasion, and reduced the volume of the tumor. Besides, iASPP overexpression could partly restore the suppressive effect of miR-184 on CNSL cell proliferation and invasive capability. We also revealed that miR-184/iASPP axis regulated the proliferation and invasion via PI3K/Akt signaling pathway, which presents a novel potential therapy for intervention of CNSL. Taken together, our findings revealed the detailed role of the miR-184/iASPP axis in CNSL and this axis might modulate the proliferation and invasion of CNSL via regulating the PI3K/Akt signaling pathway. J. Cell. Biochem. 118: 2645-2653, 2017. © 2017 Wiley Periodicals, Inc.

Epigenetic abnormalities play important roles in the pathogenesis of Hodgkin lymphoma (HL). Highly expressed class I histone acetyltransferase (HDAC) and hyper-methylation of the promoter region of tumor suppressor genes have been demonstrated in Hodgkin lymphoma. In this paper, we investigated the synergistic effects of combination treatment of chidamide, a selective HDAC inhibitor, and decitabine, a demethylation agent, for HL cell lines and explored a new strategy for treating HL. The apoptosis rates, cell cycle, mitochondrial transmembrane potentials, epigenetic changes and gene expression of HL cell lines treated with chidamide as a single agent and in combination with decitabine were tested. We found that chidamide inhibited the proliferation of HL cells through increased apoptosis. Interestingly, after combined with decitabine, the inhibition rate and apoptotic death in HL cells were significantly increased. Further studies demonstrated that when combined with decitabine the expression of acetylated histone H3 and H3K9 induced by chidamide in HL cells increased, and also the expression of tumor suppressor genes PU.1 and KLF4, which exert inhibition through apoptosis pathway. Therefore, we could come to a conclusion that chidamide and decitabine can synergistically induce apoptosis of Hodgkin lymphoma cells by up-regulating the expression of PU.1 and KLF4. These results provide a new sight in combining two different epigenetic regulatory agents for treating HL.

FIG. 1. The band structures of H (a-f) and T(g-l) types of Janus TMDs monolayers. The Fermi level is set to zero. II. METHODS

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