title: MUC1 regulates expression of multiple microRNAs involved in pancreatic tumor progression, including the miR-200c/141 cluster.
abstract: MUC1 is a transmembrane glycoprotein that modulates transcription via its cytoplasmic domain. We evaluated the capacity of MUC1 to regulate the global transcription of microRNAs in pancreatic cancer cells expressing MUC1. Results indicated that MUC1 regulated expression of at least 103 microRNAs. We evaluated further regulation of the microRNA transcript cluster miR-200c/141, which was among the most highly regulated microRNAs. We found that MUC1 directly interacted with ZEB1, a known transcriptional repressor of the miR-200c/141 cluster, at the promoter of miR-200c/141, and further reduced transcript production. These data indicate that signaling through MUC1 influences cancer progression by regulating transcription of microRNAs that are associated with the process of metastasis.
authors.affiliation: Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Mohr
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bailey
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Lewallen
authors.forename: Xiang
authors.initials: X
authors.lastname: Liu
authors.forename: Prakash
authors.initials: P
authors.lastname: Radhakrishnan
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: William
authors.initials: W
authors.lastname: Tapprich
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hollingsworth
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D018450:Disease Progression; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D035683:MicroRNAs / Q000235:genetics*; D008938:Mitosis; D008969:Molecular Sequence Data; D018396:Mucin-1 / Q000737:chemistry / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; C533895:MIRN141 microRNA, human; C533896:MIRN200 microRNA, human; C060192:MUC1 protein, human; D035683:MicroRNAs; D018396:Mucin-1; D010750:Phosphoproteins; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1