title: MiR-410 is overexpressed in liver and colorectal tumors and enhances tumor cell growth by silencing FHL1 via a direct/indirect mechanism.
abstract: FHL1 is an important tumor-suppressor that is downregulated in multiple tumors by unknown mechanisms. We demonstrated that miR-410 specifically targets the 3'UTR of FHL1. Furthermore, using DNA bisulfite modification and sequencing experiments, we demonstrated that the FHL1 promoter is hypermethylated in cancer cells. FHL1 methylation is increased upon miR-410 expression, suggesting that the regulation of FHL1 by miR-410 occurs by a dual mechanism. Using chromatin immunoprecipitation assays, we observed that miR-410 overexpression results in the increased binding of DNMT3A at the FHL1 promoter, which could explain how miR-410 regulates FHL1 methylation. Importantly, in vitro and in vivo results suggest that miR-410 may have oncogenic properties. Furthermore, both miR-410 and DNMT3A are upregulated in clinical human liver and colorectal tumors cancers. Our results suggest that miR-410 may function as an oncomiR and are consistent with its key function in regulating FHL1 in certain digestive system cancers.
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China; SDU School of Life Science, Jinan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Xiaoai
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Long
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Qinong
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Song
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D064593:Heterografts; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D060588:LIM Domain Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011485:Protein Binding
chemical_list: D020413:3' Untranslated Regions; C000717967:DNMT3A protein, human; C101149:FHL1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C568527:MIRN410 microRNA, human; D035683:MicroRNAs; D009124:Muscle Proteins; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A