Liang Xiao-Gong, Meng Wen-Tong, Hu Lian-Jie, Li Lin, Xing Hongyun, Xie Gan, Wang An-Qiong, Jia Yong-Qian
Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
Department of Hematology, Mianyang Central Hospital, Chengdu 621000, China.
J Cell Biochem. 2017 Sep;118(9):2645-2653. doi: 10.1002/jcb.25856. Epub 2017 May 15.
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.
中枢神经系统淋巴瘤（CNSL）仍然是一个诊断和治疗方面的挑战。微小RNA（miRNA）通过与靶mRNA的3'非翻译区（UTR）结合，在转录后水平调节其表达，从而抑制其翻译或促进其降解。凋亡刺激蛋白家族的癌蛋白抑制成员（iASPP）是肿瘤抑制因子p53的关键抑制剂，据报道在癌症中发挥致癌作用。我们目前的研究旨在确定miR-184/iASPP轴是否参与CNSL的增殖和侵袭。在CNSL组织中观察到miR-184水平降低。外源性miR-184抑制细胞存活和侵袭以及肿瘤体积，而抑制miR-184可逆转这一过程。miR-184显著抑制iASPP的RNA和蛋白质水平，并且iASPP的3'UTR被证明是miR-184的靶标。与正常脑组织相比，iASPP在CNSL组织中的表达上调。通过短发夹RNA干扰iASPP（shRNA iASPP）抑制iASPP可显著抑制CNSL细胞的增殖和侵袭，并减小肿瘤体积。此外，iASPP过表达可部分恢复miR-184对CNSL细胞增殖和侵袭能力的抑制作用。我们还发现miR-184/iASPP轴通过PI3K/Akt信号通路调节增殖和侵袭，这为CNSL的干预提供了一种新的潜在治疗方法。综上所述，我们的研究结果揭示了miR-184/iASPP轴在CNSL中的具体作用，并且该轴可能通过调节PI3K/Akt信号通路来调节CNSL的增殖和侵袭。《细胞生物化学杂志》118: 2645 - 2653, 2017。© 2017威利期刊公司
