title: MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus.
abstract: A locus on chromosome 9q22 harbors a SNP (rs965513) firmly associated with risk of papillary thyroid carcinoma (PTC). The locus also comprises the forkhead box E1 (FOXE1) gene, which is implicated in thyroid development, and a long noncoding RNA (lncRNA) gene, papillary thyroid cancer susceptibility candidate 2 (PTCSC2). How these might interact is not known. Here we report that PTCSC2 binds myosin-9 (MYH9). In a bidirectional promoter shared by FOXE1 and PTCSC2, MYH9 inhibits the promoter activity in both directions. This inhibition can be reversed by PTCSC2, which acts as a suppressor. RNA knockdown of FOXE1 in primary thyroid cells profoundly interferes with the p53 pathway. We propose that the interaction between the lncRNA, its binding protein MYH9, and the coding gene FOXE1 underlies the predisposition to PTC triggered by rs965513.
authors.affiliation: Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.|Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.|Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
authors.forename: Huiling
authors.initials: H
authors.lastname: He
authors.affiliation: Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.|Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Surgery, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
authors.forename: John
authors.initials: J
authors.lastname: Phay
authors.affiliation: Department of Pathology, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
authors.forename: Rulong
authors.initials: R
authors.lastname: Shen
authors.affiliation: Center for Biostatistics, The Ohio State University, Columbus, OH 43210.|Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210.
authors.forename: Lianbo
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210.
authors.forename: Baris
authors.initials: B
authors.lastname: Hancioglu
authors.affiliation: Human Cancer Genetics Program, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210; Albert.delaChapelle@osumc.edu.|Department of Cancer Biology and Genetics, The Ohio State University Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
mesh_terms: D001665:Binding Sites / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D006801:Humans; D020409:Molecular Motor Proteins / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D062085:RNA, Long Noncoding; D018995:Myosin Heavy Chains
keywords: MYH9; bidirectional promoter; lncRNA; thyroid cancer; transcriptional regulation