title: MiR-30d induces apoptosis and is regulated by the Akt/FOXO pathway in renal cell carcinoma.
abstract: MicroRNAs (miRNAs) play critical roles in tumorigenesis by modulating the expression of target gene mRNAs. However, their role in cell signaling is not well defined. In this study, we identified miR-30d as a downstream effector of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in renal cell carcinoma (RCC) cells. We show that Akt inhibition transcriptionally up-regulates miR-30d expression through activation of the transcription factor forkhead box O (FOXO) 3A. Functional analysis revealed that miR-30d overexpression suppresses cell proliferation and induces apoptosis in RCC cells, suggesting that miR-30d acts as a tumor suppressor. In searching for downstream targets of miR-30d, we found that miR-30d post-transcriptionally suppresses expression of the oncoprotein metadherin (MTDH) by destabilizing its mRNA. Furthermore, we found that FOXO down-regulates MTDH expression through up-regulating expression of miR-30d. Thus, our findings reveal a new Akt/FOXO/miR-30d/MTDH signaling transduction pathway and identify miR-30d as a tumor suppressor, providing a new potential target for the treatment of RCC.
authors: Department of Biochemistry and Molecular Biology, Health Science Center, Peking University, 38 Xueyuan Road, 100191 Beijing, China.
authors: Chenglin
authors: C
authors: Wu
authors: Bo
authors: B
authors: Jin
authors: Liting
authors: L
authors: Chen
authors: Dexiang
authors: D
authors: Zhuo
authors: Zheng
authors: Z
authors: Zhang
authors: Kan
authors: K
authors: Gong
authors: Zebin
authors: Z
authors: Mao
mesh_terms: D017209:Apoptosis; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins; D035683:MicroRNAs / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C546086:MIRN30b microRNA, human; C483039:MTDH protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt