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

First Author  Morgado-Palacin L Year  2023
Journal  Nat Commun Volume  14
Issue  1 Pages  1328
PubMed ID  36899004 Mgi Jnum  J:334066
Mgi Id  MGI:7445885 Doi  10.1038/s41467-023-36713-8
Citation  Morgado-Palacin L, et al. (2023) The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma. Nat Commun 14(1):1328
abstractText  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.
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