title: Inactivation of oncogenic cAMP-specific phosphodiesterase 4D by miR-139-5p in response to p53 activation.
abstract: Increasing evidence highlights the important roles of microRNAs in mediating p53's tumor suppression functions. Here, we report miR-139-5p as another new p53 microRNA target. p53 induced the transcription of miR-139-5p, which in turn suppressed the protein levels of phosphodiesterase 4D (PDE4D), an oncogenic protein involved in multiple tumor promoting processes. Knockdown of p53 reversed these effects. Also, overexpression of miR-139-5p decreased PDE4D levels and increased cellular cAMP levels, leading to BIM-mediated cell growth arrest. Furthermore, our analysis of human colorectal tumor specimens revealed significant inverse correlation between the expression of miR-139-5p and that of PDE4D. Finally, overexpression of miR-139-5p suppressed the growth of xenograft tumors, accompanied by decrease in PDE4D and increase in BIM. These results demonstrate that p53 inactivates oncogenic PDE4D by inducing the expression of miR-139-5p.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States.
authors.forename: Bo
authors.initials: B
authors.lastname: Cao
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Kebing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Liao
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Liao
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States.
authors.forename: Shelya X
authors.initials: SX
authors.lastname: Zeng
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Meifang
authors.initials: M
authors.lastname: He
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Lianzhou
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yulong
authors.initials: Y
authors.lastname: He
authors.affiliation: Laboratory of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, United States.
authors.forename: Hua
authors.identifier: 0000-0002-9285-7209
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000473:pathology; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4
keywords: BIM; PDE4D; apoptosis; cancer biology; human; miR-139-5p; mouse; p53; tumor suppression