title: MiR-520d-5p directly targets TWIST1 and downregulates the metastamiR miR-10b.
abstract: MicroRNAs are key players in most biological processes. Some microRNAs are involved in the genesis of tumors and are therefore termed oncomiRs, while others, termed metastamiRs, play a significant role in the formation of cancer metastases. Previously, we identified ten different cellular microRNAs that downregulate the expression of MICB, a ligand of the activating NK receptor NKG2D. Interestingly, several of the ten MICB-targeting microRNAs, such as miR-10b, are involved in tumor formation and metastasis. In this work, we identify a complex interplay between these different microRNAs. Specifically, we demonstrate that three of the MICB-targeting microRNAs: miR-20a, miR-17-5p and miR-93, also target the same site in the 3'UTR of TWIST1, a transcription factor implicated in cancer metastasis. Additionally, we show that miR-520d-5p targets a different site in the 3'UTR of TWIST1. We next show that the miR-520d-5p-mediated decrease of TWIST1 expression results in reduced expression of one of its targets, miR-10b, and in the restoration of E-Cadherin expression, which in turn results in reduced cellular motility and invasiveness. Finally, we show that miR-520d-5p leads to reduced proliferation of tumor cells, and that high levels of miR-520d-5p correlate with higher survival rates of cancer patients.
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Pinchas
authors.initials: P
authors.lastname: Tsukerman
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Yamin
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Seidel
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Saleh
authors.initials: S
authors.lastname: Khawaled
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Dominik
authors.initials: D
authors.lastname: Schmiedel
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Bar-Mag
authors.affiliation: The Lautenberg Center for General and Tumor Immunology, The Hebrew University, The BioMedical Research Institute, Israel Canada, Hadassah Medical School, Jerusalem, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D051879:Twist-Related Protein 1 / Q000096:biosynthesis*
chemical_list: C547183:MIRN10 microRNA, human; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1