title: RUNX3-mediated up-regulation of miR-29b suppresses the proliferation and migration of gastric cancer cells by targeting KDM2A.
abstract: RUNX3 is a transcriptional factor that has been shown to regulate protein-coding gene expression at the transcriptional level. However, the regulation of RUNX3 on miRNAs is not fully understood. In this study, we used miRNA microarray to identify the miRNAs that are regulated by RUNX3 and found that miR-29b showed the most up-regulation in RUNX3 over-expressed cells compared with the control cells. We used qRT-PCR to confirm the miRNA microarray results in several gastric cancer cells and found that RUNX3 could bind to the miR-29b promoter directly and cooperate with Smad3 to increase the promoter activity of miR-29b. In the clinical setting, both RUNX3 and miR-29b are down-regulated significantly in human gastric cancer tissues. A positive correlation between miR-29b and RUNX3 was found in the gastric cancer tissues. Additionally, we found that miR-29b suppressed the proliferation and metastasis of gastric cancer cells by directly targeting KDM2A. The miR-29b/KDM2A axis was involved in the RUNX3-mediated inhibition of gastric cancer cell proliferation and metastasis. Taken together, our results suggested that RUNX3-mediated up-regulation of miR-29b inhibited the proliferation and migration of gastric cancer cells by targeting KDM2A, representing a novel molecular mechanism for the tumor suppression action of RUNX3.
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, PR China.
authors: Ye
authors: Y
authors: Kong
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, PR China.
authors: Shuiyan
authors: S
authors: Zou
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, PR China.
authors: Fenghua
authors: F
authors: Yang
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, PR China.
authors: Xia
authors: X
authors: Xu
authors: The Rongjun Hospital of Qingzhou, Shandong Province, PR China.
authors: Wenhong
authors: W
authors: Bu
authors: Department of Microbiology/Key Laboratory for Experimental Teratology of Chinese Ministry of Education, School of Medicine, Shandong University, Jinan, PR China.
authors: Jihui
authors: J
authors: Jia
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, PR China. Electronic address: liuzhifang@sdu.edu.cn.
authors: Zhifang
authors: Z
authors: Liu
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D044783:F-Box Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; C493729:Runx3 protein, human; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D056484:Jumonji Domain-Containing Histone Demethylases; C534524:KDM2A protein, human
keywords: Gastric cancer; KDM2A; RUNX3; Smad3; miR-29b