title: An intramolecular G-quadruplex structure formed in the human MET promoter region and its biological relevance.
abstract: Previous studies have shown that promoter regions of many proto-oncogenes can fold into G-quadruplexes, which are potentially involved in the regulation of genes. Bioinformatics analysis suggested that there was a G-rich sequence within -48 to -26 region of the human MET promoter (named Pu23WT). In this study, we proved that Pu23WT adopted an intramolecular parallel G-quadruplex structure under physiological conditions in vitro, and the cationic porphyrin TMPyP4 enhanced the stability of the Pu23WT G-quadruplex. To better understand the functions of Pu23WT in the MET expression, we performed a series of analysis on several cancer cells. Experimental data revealed that TMPyP4 treatment attenuated the expression of MET in HepG2, BGC823, and U87MG cells, resulting in the cellular proliferation inhibition, G1 phase cell cycle arrest and cell migration retardation. ChIP assay results indicated that TMPyP4 probably prohibited the Pu23WT G-quadruplex from binding to the activator Sp1, which could be one of the mechanisms that led to the transcription inhibition of MET gene. It is the first study on the G-quadruplex structure in the human MET promoter and its functions in cancer cells. We believe that this structure is a potential target for anticancer treatment.
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning, China.
authors.forename: Yifu
authors.initials: Y
authors.lastname: Guan
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054856:G-Quadruplexes / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011166:Porphyrins / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000378:metabolism
chemical_list: D011166:Porphyrins; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C021096:tetra(4-N-methylpyridyl)porphine; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met
keywords: G-quadruplex structure; MET promoter; TMPyP4; anticancer treatment