title: miR-6734 Up-Regulates p21 Gene Expression and Induces Cell Cycle Arrest and Apoptosis in Colon Cancer Cells.
abstract: Recently, microRNAs have been implicated in the regulation of gene expression in terms of both gene silencing and gene activation. Here, we investigated the effects of miR-6734, which has a sequence homology with a specific region of p21WAF1/CIP1 (p21) promoter, on cancer cell growth and the mechanisms involved in this effect. miR-6734 up-regulated p21 expression at both mRNA and protein levels and chromatin immunoprecipitation analysis using biotin-labeled miR-6734 confirmed the association of miR-6734 with p21 promoter. Moreover, miR-6734 inhibited cancer cell growth and induced cell cycle arrest and apoptosis in HCT-116 cells, which was abolished by knockdown of p21. The phosphorylation of Rb and the cleavage of caspase 3 and PARP were suppressed by miR-6734 transfection in HCT-116 cells and these effects were also reversed by p21 knockdown. In addition, miR-6734 transfection caused prolonged induction of p21 gene and modification of histones in p21 promoter, which are typical aspects of a phenomenon referred to as RNA activation (RNAa). Collectively, our results demonstrated that miR-6734 inhibits the growth of colon cancer cells by up-regulating p21 gene expression and subsequent induction of cell cycle arrest and apoptosis, suggesting its role as an important endogenous regulator of cancer cell proliferation and survival.
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Moo Rim
authors: MR
authors: Kang
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Ki Hwan
authors: KH
authors: Park
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Jeong-Ook
authors: JO
authors: Yang
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Chang Woo
authors: CW
authors: Lee
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Soo Jin
authors: SJ
authors: Oh
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Jieun
authors: J
authors: Yun
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Myeong Youl
authors: MY
authors: Lee
authors: College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea.
authors: Sang-Bae
authors: SB
authors: Han
authors: Bio-Evaluation Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea.
authors: Jong Soon
authors: JS
authors: Kang
mesh_terms: D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006657:Histones; C000622039:MIRN6734 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D024101:Mitochondrial Proteins