The Hormel Institute, University of Minnesota, Austin, MN, USA.
Department of Dermatology, Columbia University, New York, NY, USA.
Exp Dermatol. 2020 Oct;29(10):1021-1026. doi: 10.1111/exd.14174. Epub 2020 Sep 22.
The high mobility group AT-hook 2 (HMGA2) gene encodes a transcription factor that is expressed during embryonic development but down-regulated in adult tissues. Its re-expression in adult tissues is often associated with tumorigenesis. In this study, we found that HMGA2 is highly expressed in human cutaneous squamous cell carcinoma (SCC) cell lines and primary SCC tumors, but not in adjacent normal skin. In non-ultraviolet (UV)-irradiated mouse skin, baseline Hmga2 expression was detected in the epidermis but not in hair follicles. Following chronic UV exposure, we found activation of Hmga2 in hair follicles. UV-induced mouse skin SCC tumors displayed a ubiquitous increase in Hmga2 expression compared to non-tumor-bearing adjacent skin. In human SCC cells, decreased HMGA2 expression was linked with reduced cell proliferation following depletion of FOXM1 and TRIP13, two UV master regulator genes. Taken together, these findings highlight an important biomarker function of HMGA2 expression in UV-induced skin tumorigenesis and cell proliferation.
高迁移率族 AT 钩 2（HMGA2）基因编码一种转录因子，在胚胎发育过程中表达，但在成年组织中下调。其在成年组织中的重新表达常与肿瘤发生有关。在这项研究中，我们发现 HMGA2 在人皮肤鳞状细胞癌（SCC）细胞系和原发性 SCC 肿瘤中高度表达，但在相邻正常皮肤中不表达。在非紫外线（UV）照射的小鼠皮肤中，表皮中检测到 Hmga2 的基础表达，但毛囊中没有。在慢性 UV 暴露后，我们发现毛囊中 Hmga2 的激活。与非肿瘤携带相邻皮肤相比，UV 诱导的小鼠皮肤 SCC 肿瘤显示 Hmga2 表达普遍增加。在人 SCC 细胞中，FOXM1 和 TRIP13（两个 UV 主调控基因）耗竭后，HMGA2 表达减少与细胞增殖减少有关。综上所述，这些发现强调了 HMGA2 表达在 UV 诱导的皮肤肿瘤发生和细胞增殖中的重要生物标志物功能。
