Choi Sangyong, Sathe Adwait, Mathé Ewy, Xing Chao, Pan Zui
College of Nursing and Health Innovation, University of Texas at Arlington, Arlington, TX, United States.
Department of Nutritional Sciences, College of Agriculture, Health and Natural Resources, University of Connecticut, Storrs, CT, United States.
Front Oncol. 2021 Oct 15;11:724687. doi: 10.3389/fonc.2021.724687. eCollection 2021.
Abnormal genetic and epigenetic modifications play a key role in esophageal cancer. By Assay for Transposase-Accessible Chromatin by sequencing (ATAC-seq), this study compared chromatin accessibility landscapes among two esophageal squamous cell carcinoma (ESCC) cell lines, KYSE-30 and KYSE-150, and a non-cancerous esophageal epithelial cell line, HET-1A. Data showed that hyper-accessible regions in ESCC cells contained genes related with cancer hallmarks, such as epidermal growth factor receptor (EGFR). Multi-omics analysis and digital-droplet PCR results demonstrated that several non-coding RNAs in EGFR upstream were upregulated in ESCC cells. Among them, one appeared to act as an enhancer RNA responsible for EGFR overexpression. Further motif analysis and pharmacological data suggested that AP-1 family transcription factors were able to bind the hyper-accessible regions and thus to regulate cancer cell proliferation and migration. This study discovered a putative enhancer RNA for EGFR gene and the reliance of ESCC on AP-1 transcription factor.
异常的基因和表观遗传修饰在食管癌中起关键作用。通过测序转座酶可及染色质分析（ATAC-seq），本研究比较了两种食管鳞状细胞癌（ESCC）细胞系KYSE-30和KYSE-150以及一种非癌食管上皮细胞系HET-1A之间的染色质可及性图谱。数据显示，ESCC细胞中的高可及性区域包含与癌症特征相关的基因，如表皮生长因子受体（EGFR）。多组学分析和数字液滴PCR结果表明，ESCC细胞中EGFR上游的几种非编码RNA上调。其中一种似乎作为增强子RNA负责EGFR的过表达。进一步的基序分析和药理学数据表明，AP-1家族转录因子能够结合高可及性区域，从而调节癌细胞的增殖和迁移。本研究发现了一个推测的EGFR基因增强子RNA以及ESCC对AP-1转录因子的依赖性。
