title: MicroRNA-184 Modulates Human Central Nervous System Lymphoma Cells Growth and Invasion by Targeting iASPP.
abstract: 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.
authors.affiliation: Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.|Department of Hematology, Mianyang Central Hospital, Chengdu 621000, China.
authors.forename: Xiao-Gong
authors.initials: XG
authors.lastname: Liang
authors.affiliation: Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Wen-Tong
authors.initials: WT
authors.lastname: Meng
authors.affiliation: Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lian-Jie
authors.initials: LJ
authors.lastname: Hu
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hematology, Affiliated Southwest Medical University, Luzhou 646000, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Xing
authors.affiliation: Department of Pathology, Mianyang Central Hospital, Mianyang 621000, China.
authors.forename: Gan
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Pathology, Mianyang Central Hospital, Mianyang 621000, China.
authors.forename: An-Qiong
authors.initials: AQ
authors.lastname: Wang
authors.affiliation: Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yong-Qian
authors.initials: YQ
authors.lastname: Jia
mesh_terms: D020413:3' Untranslated Regions; D049109:Cell Proliferation; D016543:Central Nervous System Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D020413:3' Untranslated Regions; D047908:Intracellular Signaling Peptides and Proteins; C534424:MIRN184 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; C119612:PPP1R13L protein, human; D012334:RNA, Neoplasm; D012097:Repressor Proteins
keywords: ASPP; CENTRAL NERVOUS SYSTEM LYMPHOMA; INVASION; MIR-184; PROLIFERATION