Epigenetic Alterations in Keratinocyte Carcinoma.
Epigenetic Alterations in Keratinocyte Carcinoma.
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DOI：
10.1016/j.jid.2020.10.018
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Asgari MM
中科院分区：
文献类型：
--
作者：
Yao Q;Epstein CB;Banskota S;Issner R;Kim Y;Bernstein BE;Pinello L;Asgari MM
基底细胞癌（BCC）和鳞状细胞癌（SCC）都来源于表皮角质形成细胞，但表型不同。为了提高对角质形成细胞致癌作用的理解，了解表观遗传学改变，特别是那些控制基因表达的改变是至关重要的。我们通过对11例接受莫氏手术的患者（5例基底细胞癌和6例鳞状细胞癌）进行配对的肿瘤-正常对照，检测了增强子相关组蛋白乙酰化标记H3 K27 ac的变化。我们的分析基于匹配的肿瘤-正常对之间的差异H3 K27 ac峰揭示了癌症特异性增强子。我们还发现了在角质形成细胞癌中可能改变的生物学途径，包括在BCC中富集的表皮发育和Wnt信号传导途径，以及在SCC中富集的免疫应答和细胞活化途径。我们还观察到涉及基底细胞癌发病机制中SMAD和JDP 2以及SCC发病机制中FOXP 1的转录因子的富集。基于这些发现，我们优先考虑了三个具有推定调控事件的位点：BCC中的FGFR 2增强子，SCC中FOXP 1的基因内调控，以及两种亚型中的WNT 5A启动子，并利用已发表的基因表达数据验证了我们的发现。我们的研究结果突出了组蛋白修饰中独特和共享的表观遗传学改变以及可能影响不同致癌途径的BCC和SCC的潜在调节剂，为靶向药物的发现铺平了道路。
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are both derived from epidermal keratinocytes but phenotypically diverge. To improve understanding of keratinocyte carcinogenesis, it is critical to understand epigenetic alterations, particularly those that govern gene expression. We examined changes to the enhancer-associated histone acetylation mark H3K27ac by mapping matched tumor-normal pairs from 11 patients (5 with BCC and 6 with SCC) undergoing Mohs surgery. Our analysis uncovered cancer-specific enhancers based on differential H3K27ac peaks between matched tumor-normal pairs. We also uncovered biologic pathways potentially altered in keratinocyte carcinoma including enriched epidermal development and Wnt signaling pathways enriched in BCCs, and enriched immune response and cell activation pathways in SCCs. We also observed enrichment of transcription factors that implicated SMAD and JDP2 in BCC pathogenesis and FOXP1 in SCC pathogenesis. Based on these findings, we prioritized three loci with putative regulation events: FGFR2 enhancer in BCC, intragenic regulation of FOXP1 in SCC, and WNT5A promoter in both subtypes and validated our findings with published gene expression data. Our findings highlight unique and shared epigenetic alterations in histone modifications and potential regulators for BCCs and SCCs that likely impact divergent oncogenic pathways, paving the way for targeted drug discoveries.
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Wnt和HH信号通路之间的串扰。
DOI：
10.3390/ijerph15071442
发表时间：
2018-07-09
影响因子：
--
作者：
Noubissi FK;Yedjou CG;Spiegelman VS;Tchounwou PB
通讯作者：
Tchounwou PB
影响因子：
3.7
作者：
Brinkhuizen, Tjinta;van den Hurk, Karin;van Steensel, Maurice A. M.
通讯作者：
van Steensel, Maurice A. M.
影响因子：
10.3
作者：
Goldberg, M.;Rummelt, C.;Ballhausen, W. G.
通讯作者：
Ballhausen, W. G.
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
8
作者：
Salto-Tellez, M.;Peh, B. K.;Ito, Y.
通讯作者：
Ito, Y.