Genetics and Cancer Research Unit, Hospital Juárez de México (HJM), 07760 Mexico City, Mexico.
Oncogenomic Department, Instituto Nacional de Medicina Genómica (INMEGEN), 14610 Mexico City, Mexico.
Biomed Res Int. 2017;2017:7868645. doi: 10.1155/2017/7868645. Epub 2017 Oct 10.
The aim of this work was to compare the early gene expression profiles in the skin of HPV16-E6 transgenic mice regulated by the E6 PDZ-binding motif.
The global transcriptional profiles in dorsal skin biopsies from K14E6 and K14E6Δ146-151 transgenic mice were compared using microarrays. Relevant genes obtained from the most differentially expressed processes were further examined by RT-qPCR, in situ RT-PCR, Western blot, or immunofluorescence.
The transcriptomic landscape of K14E6 versus K14E6Δ146-151 shows that the most affected expression profiles were those related to keratinocyte differentiation, stem cell maintenance, and keratinization. Additionally, downregulation of epidermal stemness markers such as K15 and CD34, as well as the upregulation of cytokeratin 6b, appeared to be dependent on the E6 PDZ-binding motif. Finally, wound healing, a physiological process linked to stemness, is impaired in the K14E6 mice compared to K14E6Δ146-151.
The E6 PDZ-binding motif appears to affect stemness and keratinization during early stages of skin carcinogenesis. As E6 plays a significant role in HPV-induced skin carcinogenesis, the K14E6 versus K14E6Δ146-151 transcriptional profile provides a source of valuable data to uncover novel E6 functions in the skin.
本研究旨在比较 HPV16-E6 转染小鼠皮肤中受 E6 PDZ 结合基序调控的早期基因表达谱。
通过微阵列比较 K14E6 和 K14E6Δ146-151 转基因小鼠背部皮肤活检的全基因组转录谱。从差异表达最显著的过程中获得的相关基因，进一步通过 RT-qPCR、原位 RT-PCR、Western blot 或免疫荧光进行检测。
K14E6 与 K14E6Δ146-151 的转录组图谱表明，受影响最显著的表达谱与角蛋白细胞分化、干细胞维持和角化有关。此外，表皮干细胞标志物如 K15 和 CD34 的下调，以及细胞角蛋白 6b 的上调，似乎依赖于 E6 PDZ 结合基序。最后，与 K14E6Δ146-151 相比，K14E6 小鼠的伤口愈合（与干细胞有关的生理过程）受损。
E6 PDZ 结合基序似乎在皮肤癌发生的早期阶段影响干细胞特性和角化。由于 E6 在 HPV 诱导的皮肤癌发生中起着重要作用，K14E6 与 K14E6Δ146-151 的转录谱为揭示 E6 在皮肤中的新功能提供了有价值的数据来源。
