title: Tumor suppressor PDCD4 modulates miR-184-mediated direct suppression of C-MYC and BCL2 blocking cell growth and survival in nasopharyngeal carcinoma.
abstract: Programmed cell death 4 (PDCD4), a novel tumor suppressor, inhibits cell proliferation, migration and invasion as well as promotes cell apoptosis in tumors. However, the molecular mechanism of its tumor-suppressive function remains largely unknown in tumors including nasopharyngeal carcinoma (NPC). In this study, downregulated PDCD4 expression was significantly associated with the status of NPC progression and poor prognosis. PDCD4 markedly suppressed the ability of cell proliferation and cell survival by modulating C-MYC-controlled cell cycle and BCL-2-mediated mitochondrion apoptosis resistance signals, and oncogenic transcription factor C-JUN in NPC. Furthermore, miR-184, a tumor-suppressive miRNA modulated by PDCD4 directly targeting BCL2 and C-MYC, participated in PDCD4-mediated suppression of cell proliferation and survival in NPC. Further, we found that PDCD4 decreased the binding of C-Jun to the AP-1 element on the miR-184 promoter regions by PI3K/AKT/JNK/C-Jun pathway and stimulated miR-184 expression. In clinical fresh specimens, reduced PDCD4 mRNA level was positively correlated with miR-184 expression in NPC. Our studies are the first to demonstrate that PDCD4 as tumor suppressor regulated miR-184-mediated direct targeting of BCL2 and C-MYC via PI3K/AKT and JNK/C-Jun pathway attenuating cell proliferation and survival in NPC.
authors.affiliation: 1] Department of Pathology, Basic School, Guangzhou Medical University, Guangzhou 510182, PR China [2] Cancer Research Institute, Southern Medical University, Guangzhou 510515, PR China [3] Institute of Respiratory Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524000, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhen
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.forename: Huiling
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yu
authors.forename: Qiangyun
authors.initials: Q
authors.lastname: Wu
authors.forename: Shengni
authors.initials: S
authors.lastname: Hua
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Long
authors.forename: Qingping
authors.initials: Q
authors.lastname: Jiang
authors.forename: Ye
authors.initials: Y
authors.lastname: Song
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Menyang
authors.initials: M
authors.lastname: Zhao
authors.forename: Qiaofen
authors.initials: Q
authors.lastname: Fu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lyu
authors.forename: Yiyu
authors.initials: Y
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Fan
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D002277:Carcinoma; D002453:Cell Cycle / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C534424:MIRN184 microRNA, human; D035683:MicroRNAs; C114487:PDCD4 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases