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The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma

Author

Listed:
  • Lucia Morgado-Palacin

    (Columbia University)

  • Jessie A. Brown

    (Columbia University)

  • Thomas F. Martinez

    (University of California)

  • Juana M. Garcia-Pedrero

    (Hospital Universitario Central de Asturias (HUCA)
    Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo
    Ciber de Cáncer, CIBERONC)

  • Farhad Forouhar

    (Columbia University)

  • S. Aidan Quinn

    (Columbia University)

  • Clara Reglero

    (Columbia University)

  • Joan Vaughan

    (Salk Institute for Biological Studies)

  • Yasamin Hajy Heydary

    (University of California)

  • Cynthia Donaldson

    (Salk Institute for Biological Studies)

  • Sandra Rodriguez-Perales

    (Centro Nacional de Investigaciones Oncológicas (CNIO))

  • Eva Allonca

    (Hospital Universitario Central de Asturias (HUCA)
    Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo)

  • Rocio Granda-Diaz

    (Hospital Universitario Central de Asturias (HUCA)
    Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo
    Ciber de Cáncer, CIBERONC)

  • Agustin F. Fernandez

    (Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo
    Nanomaterials and Nanotechnology Research Center (CINN-CSIC)
    University of Oviedo)

  • Mario F. Fraga

    (Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo
    Nanomaterials and Nanotechnology Research Center (CINN-CSIC)
    University of Oviedo)

  • Arianna L. Kim

    (Columbia University Irving Medical Center)

  • Jorge Santos-Juanes

    (Hospital Universitario Central de Asturias (HUCA)
    University of Oviedo Medical School)

  • David M. Owens

    (Columbia University Irving Medical Center
    Columbia University Irving Medical Center)

  • Juan P. Rodrigo

    (Hospital Universitario Central de Asturias (HUCA)
    Instituto de Investigación Sanitaria del Principado de Asturias (ISPA)
    Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo
    Ciber de Cáncer, CIBERONC)

  • Alan Saghatelian

    (Salk Institute for Biological Studies)

  • Adolfo A. Ferrando

    (Columbia University
    University of Oviedo Medical School
    Columbia University)

Abstract

The TINCR (Terminal differentiation-Induced Non-Coding RNA) gene is selectively expressed in epithelium tissues and is involved in the control of human epidermal differentiation and wound healing. Despite its initial report as a long non-coding RNA, the TINCR locus codes for a highly conserved ubiquitin-like microprotein associated with keratinocyte differentiation. Here we report the identification of TINCR as a tumor suppressor in squamous cell carcinoma (SCC). TINCR is upregulated by UV-induced DNA damage in a TP53-dependent manner in human keratinocytes. Decreased TINCR protein expression is prevalently found in skin and head and neck squamous cell tumors and TINCR expression suppresses the growth of SCC cells in vitro and in vivo. Consistently, Tincr knockout mice show accelerated tumor development following UVB skin carcinogenesis and increased penetrance of invasive SCCs. Finally, genetic analyses identify loss-of-function mutations and deletions encompassing the TINCR gene in SCC clinical samples supporting a tumor suppressor role in human cancer. Altogether, these results demonstrate a role for TINCR as protein coding tumor suppressor gene recurrently lost in squamous cell carcinomas.

Suggested Citation

  • Lucia Morgado-Palacin & Jessie A. Brown & Thomas F. Martinez & Juana M. Garcia-Pedrero & Farhad Forouhar & S. Aidan Quinn & Clara Reglero & Joan Vaughan & Yasamin Hajy Heydary & Cynthia Donaldson & Sa, 2023. "The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36713-8
    DOI: 10.1038/s41467-023-36713-8
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    References listed on IDEAS

    as
    1. Olga Boix & Marion Martinez & Santiago Vidal & Marta Giménez-Alejandre & Lluís Palenzuela & Laura Lorenzo-Sanz & Laura Quevedo & Olivier Moscoso & Jorge Ruiz-Orera & Pilar Ximénez-Embún & Nikaoly Ciri, 2022. "pTINCR microprotein promotes epithelial differentiation and suppresses tumor growth through CDC42 SUMOylation and activation," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    2. Markus Kretz & Zurab Siprashvili & Ci Chu & Dan E. Webster & Ashley Zehnder & Kun Qu & Carolyn S. Lee & Ross J. Flockhart & Abigail F. Groff & Jennifer Chow & Danielle Johnston & Grace E. Kim & Robert, 2013. "Control of somatic tissue differentiation by the long non-coding RNA TINCR," Nature, Nature, vol. 493(7431), pages 231-235, January.
    3. Gareth J. Inman & Jun Wang & Ai Nagano & Ludmil B. Alexandrov & Karin J. Purdie & Richard G. Taylor & Victoria Sherwood & Jason Thomson & Sarah Hogan & Lindsay C. Spender & Andrew P. South & Michael S, 2018. "The genomic landscape of cutaneous SCC reveals drivers and a novel azathioprine associated mutational signature," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
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