The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma.
The TINCR ubiquitin-like microprotein is a tumor suppressor in squamous cell carcinoma.
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DOI：
10.1038/s41467-023-36713-8
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发表时间：
2023-03-10
影响因子：
16.6
通讯作者：
Ferrando, Adolfo A.
中科院分区：
文献类型：
--
作者：
Morgado-Palacin, Lucia;Brown, Jessie A.;Martinez, Thomas F.;Garcia-Pedrero, Juana M.;Forouhar, Farhad;Quinn, S. Aidan;Reglero, Clara;Vaughan, Joan;Heydary, Yasamin Hajy;Donaldson, Cynthia;Rodriguez-Perales, Sandra;Allonca, Eva;Granda-Diaz, Rocio;Fernandez, Agustin F.;Fraga, Mario F.;Kim, Arianna L.;Santos-Juanes, Jorge;Owens, David M.;Rodrigo, Juan P.;Saghatelian, Alan;Ferrando, Adolfo A.
TINCR（终末分化诱导的非编码RNA）基因选择性地在上皮组织中表达，并且参与人表皮分化和伤口愈合的控制。尽管TINCR基因座最初被报道为长的非编码RNA，但其编码与角质形成细胞分化相关的高度保守的泛素样微蛋白。在这里，我们报告TINCR作为鳞状细胞癌（SCC）的肿瘤抑制因子的鉴定。在人角质形成细胞中，TINCR以TP 53依赖性方式被UV诱导的DNA损伤上调。在皮肤和头颈部鳞状细胞肿瘤中发现TINCR蛋白表达降低，并且TINCR表达在体外和体内抑制SCC细胞的生长。因此，Tincr基因敲除小鼠在UVB皮肤致癌作用后显示出加速的肿瘤发展和增加的侵袭性SCC的转移率。最后，遗传分析确定了SCC临床样本中包含TINCR基因的功能缺失突变和缺失，支持其在人类癌症中的肿瘤抑制作用。总之，这些结果证明了TINCR作为蛋白编码肿瘤抑制基因在鳞状细胞癌中反复丢失的作用。TINCR编码在复层上皮中表达的p53调节的泛素样微蛋白。Tincr缺失促进小鼠UVB诱导的皮肤癌发生，人类鳞状细胞癌中的缺失和突变支持肿瘤抑制作用。
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.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
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作者：
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作者：
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通讯作者：
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