title: miR675 upregulates long noncoding RNA H19 through activating EGR1 in human liver cancer.
abstract: microRNAs (miRNAs) are short non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miR675, embedded in H19's first exon, had been linked to the development of human cancers. Herein, we demonstrate miR675 overexpression promotes and silencing miR675 attenuated liver cancer cell growth in vitro and in vivo. Mechanistically, miR675 inhibits the heterochromatin1 isoform HP1α expression in human liver cancer cells which causes a dramatically decrease of the total histone H3 lysine 9 trimethylation (H3K9me3) , histone H3 lysine 27 trimethylation (H3K27me3) and a increase of histone H3 lysine 27 acetylation(H3K27Ac).Notably, a significant reduction of the H3K9me3 and H3K27me3 and the increment of H3K27Ac occupancy on the promoter region of EGR1 triggers EGR1 transcription, translation, sumoylation and activation which upregulates lincRNA H19. Strikingly, H19 may induce and activate tumor-specific pyruvate kinase M2 (PKM2) which is essential for the Warburg effect in its dimer and for gene expression in its teramer during tumorigenesis. Our results imply that miR675 is involved in the epigenetic regulation of H3K9me3, H3k27me3 and H3K27Ac for gene expression and function during hepatocarcinogenesis (e.g.C-myc,Pim1,Ras,CyclinD1,RB1).These findings sheds light on the significance of miR675-HP1α-EGR1-H19-PKM2 cascade signaling pathway in liver cancer.
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Li
authors.affiliation: School of Medicine, Tongji University, Shanghai, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Medicine, Tongji University, Shanghai, China.
authors.forename: Song
authors.initials: S
authors.lastname: Jia
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Mengying
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: An
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Lu
mesh_terms: D000107:Acetylation; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D000090266:Chromobox Protein Homolog 5; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C000715594:CBX5 protein, human; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C094335:H19 long non-coding RNA; C548379:MIRN675 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D000090266:Chromobox Protein Homolog 5
keywords: early growth response protein 1; hepatoma; lincRNA H19; microRNA675; pyruvate kinase M2