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

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. TINCR encodes a p53-regulated ubiquitin-like microprotein expressed in stratified epithelia. Tincr loss promotes UVB-induced skin carcinogenesis in mice and deletions and mutations in human squamous cell carcinoma support a tumor suppressor role.

Automated summary

The TINCR gene plays an important role in epithelium tissues, controlling human epidermal differentiation and wound healing. It has been found to have tumor suppressor properties in squamous cell carcinoma (SCC), being upregulated by UV-induced DNA damage in a TP53-dependent manner. TINCR expression inhibits the growth of SCC cells in vitro and in vivo, and deletion or mutation of the TINCR gene has been observed in SCC clinical samples. These findings highlight the significance of TINCR as a protein coding tumor suppressor gene lost in squamous cell carcinomas.