YEATS2 promotes malignant phenotypes of esophageal squamous cell carcinoma via H3K27ac activated-IL6ST

Xiaolong Cheng ^* Yuanfang Zhai Fanyu Zhang Xiaoyu Shi Siwei Zou Xiaoling Hu Chengyuan Shan Ling Zhang Zou Binbin Xin Yang Pengzhou Kong

• Shanxi Medical University, Taiyuan, China

Histone acetylation modifications can regulate gene transcription and play crucial roles in multiple tumorigeneses processes. YEATS domain proteins are one important type of acetylation readers. We have found significant mutations and copy number amplifications of YEATS domain containing 2 (YEATS2) gene in esophageal squamous cell carcinoma (ESCC) through whole genome sequencing (WGS). However, the function and molecular mechanism of YEATS2 in ESCC remain elusive. ESCC patients with copy number amplification of YEATS2 had shorter postoperative survival. Furthermore, YEATS2 expression was positively correlated with copy number amplification. We have also found that YEATS2 expression was significantly upregulated in ESCC tissues and was correlated closely with the differentiation degree of ESCC cells. The results of in vivo and in vitro experiments revealed that YEATS2 enhanced the abilities of ESCC cells to proliferate and migrate. Mechanistically, YEATS2 activated NF-κB signaling to promote ESCC progression. YEATS2 and H3K27 acetylation (H3K27ac) were both enriched in the promoter region of IL6ST, which is involved in the regulation of YEATS2 on NF-κB signaling. Additionally, YEATS2 could recruit TAF15 and KAT5 to enhance H3K27ac enrichment in the promoter region of IL6ST to regulate its expression. In conclusion, YEATS2 might function as a potential driver gene and a potential therapeutic target in ESCC.