组蛋白甲基化通常被认为通过调节癌相关基因在多种癌症中发挥重要作用。本研究旨在研究H3K27me3介导的抑癌基因SFRP1的失活作用及其在食管鳞状细胞癌（ESCC）中的功能。我们对ESCC细胞中富含H3K27me3的基因组DNA片段进行了ChIP-seq筛选，以筛选出可能被H3K27me3调节的抑癌基因。使用ChIP-qPCR和Western blot探索了H3K27me3与SFRP1之间的调节机制。使用定量实时聚合酶链反应（q-PCR）评估了29对ESCC手术样本中SFRP1的表达水平。利用细胞增殖实验、集落形成实验和划痕愈合实验检测了SFRP1在ESCC中的功能。我们的研究结果表明，H3K27me3广泛分布于ESCC细胞的基因组中。具体而言，我们发现H3K27me3沉积在SFRP1启动子上游区域，并使SFRP1表达失活。此外，我们发现ESCC组织中SFRP1明显下调，与邻近非肿瘤组织相比，SFRP1表达与TNM分期和淋巴结转移显著相关。体外细胞实验表明，过表达SFRP1显著抑制了细胞增殖，并与细胞核内β-连接蛋白的表达负相关。我们的研究揭示了一个以前未被发现的发现，即H3K27me3介导的SFRP1通过失活Wnt/β-连接蛋白信号通路抑制了ESCC的细胞增殖。©2023年。作者（们），在Springer Science+Business Media，LLC的独家许可下，隶属于Springer Nature。

Histone methylations are generally considered to play an important role in multiple cancers by regulating cancer-related genes.This study aims to investigate the effects of H3K27me3-mediated inactivation of tumor suppressor gene SFRP1 and its function in esophageal squamous cell carcinoma (ESCC).We performed ChIP-seq on H3K27me3-enriched genomic DNA fragments in ESCC cells to screen out tumor suppressor genes that may be regulated by H3K27me3. ChIP-qPCR and Western blot were employed to explore the regulating mechanisms between H3K27me3 and SFRP1. Expression level of SFRP1 was assessed by quantitative real-time polymerase chain reaction (q-PCR) in 29 pairs of ESCC surgical samples. SFRP1 function in ESCC cells were detected by cell proliferation assay, colony formation assay and wound-healing assay.Our results indicated that H3K27me3 was widely distributed in the genome of ESCC cells. Specifically, we found that H3K27me3 deposited on the upstream region of SFRP1 promoter and inactivated SFRP1 expression. Furthermore, we found SFRP1 was significantly down-regulated in ESCC tissues compared with the adjacent non-tumor tissues, and SFRP1 expression was significantly associated with TNM stage and lymph node metastasis. In vitro cell-based assay indicated that over-expression of SFRP1 significantly suppressed cell proliferation and negatively correlated with the expression of β-catenin in the nucleus.Our study revealed a previously unrecognized finding that H3K27me3-mediated SFRP1 inhibit the cell proliferation of ESCC through inactivation of Wnt/β-catenin signaling pathway.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.