title: Loss of connective tissue growth factor as an unfavorable prognosis factor activates miR-18b by PI3K/AKT/C-Jun and C-Myc and promotes cell growth in nasopharyngeal carcinoma.
abstract: Connective tissue growth factor (CTGF) has different roles in different types of cancer. However, the involvement and molecular basis of CTGF in tumor progression and prognosis of human nasopharyngeal carcinoma (NPC) have almost never been reported. In this study, we observed that downregulated CTGF expression was significantly associated with NPC progression and poor prognosis. Knockdown of CTGF markedly elevated the ability of cell proliferation in vivo and in vitro. Subsequently, we discovered that the reduction of CTGF increased the expression of miR-18b, an oncomir-promoting cell proliferation. Further, we discovered that attenuated CTGF-mediated upregulation of miR-18b was dependent on the increased binding of transcription factors Jun proto-oncogene (C-Jun) and v-Myc myelocytomatosis viral oncogene homolog (C-Myc) to miR-18b promoter region via phosphoinositide 3-kinase (PI3K)/AKT pathway. Finally, we further found that miR-18b directly suppressed the expression of CTGF in NPC. In clinical fresh specimens, miR-18b was widely overexpressed and inversely correlated with CTGF expression in NPC. Our studies are the first to demonstrate that reduced CTGF as an unfavorable prognosis factor mediates the activation of miR-18b, an oncomir directly suppresses CTGF expression, by PI3K/AKT/C-Jun and C-Myc and promotes cell growth of NPC.
authors.affiliation: Department of Oncology, Cancer Research Institute, Southern Medical University, Guangzhou, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Yu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhen
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.forename: E
authors.initials: E
authors.lastname: Wang
authors.forename: F M
authors.initials: FM
authors.lastname: Marincola
authors.forename: C
authors.initials: C
authors.lastname: Mai
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: Wei
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.forename: X
authors.initials: X
authors.lastname: Lyu
authors.forename: Y
authors.initials: Y
authors.lastname: Ye
authors.forename: L
authors.initials: L
authors.lastname: Cai
authors.forename: Q
authors.initials: Q
authors.lastname: Wu
authors.forename: M
authors.initials: M
authors.lastname: Zhao
authors.forename: S
authors.initials: S
authors.lastname: Hua
authors.forename: Q
authors.initials: Q
authors.lastname: Fu
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: K
authors.initials: K
authors.lastname: Yao
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Fang
mesh_terms: D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D055513:Connective Tissue Growth Factor; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C000715470:MAS1 protein, human; C581632:MIRN18 microRNA, human