State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Thorac Cancer. 2021 Dec;12(24):3370-3379. doi: 10.1111/1759-7714.14211. Epub 2021 Nov 2.
Esophageal cancer is currently the eighth most common tumor in the world and a leading cause of cancer death. SULT2B1 plays crucial roles in tumorigenesis. The purpose of this study is to explore the role of SULT2B1 in esophageal squamous cell carcinoma (ESCC).
The expression of SULT2B1 and its clinicopathological characteristics were evaluated in ESCC cohorts. Bisulfite genomic sequencing and methylation specific PCR were used to detect the promoter hypermethylation of the SULT2B1 gene. The effects of SULT2B1 on the biological characters of ESCC cells were identified on functional assays. Subcutaneous xenograft models revealed the role of SULT2B1 in vivo with tumor growth. RNA-Seq analysis and qRT-PCR were performed to recognize the targeted effect of SULT2B1 on PER1.
SULT2B1 was not expressed or at a low level in most patients with ESCC or in ESCC cell lines, and this was accompanied by poor clinical prognosis. Furthermore, the downregulation of SULT2B1 occurred in promoter hypermethylation. According to the functional results, overexpression of SULT2B1 could inhibit tumoral proliferation in vitro and retard tumor growth in vivo, whereas SULT2B1 knockdown could accelerate ESCC progression. Mechanistically, SULT2B1 targeted PER1 at the mRNA level during post-transcriptional regulation. Finally, PER1 was verified as a suppressor and poor-prognosis factor in ESCC.
SULT2B1 loss is a consequence owing to its ability to promote hypermethylation. In addition, it serves as a suppressor and poor-prognosis factor because of the post-transcriptional regulation of PER1 in ESCC.
食管癌是目前全球第八大常见肿瘤，也是癌症死亡的主要原因。SULT2B1 在肿瘤发生中起着关键作用。本研究旨在探讨 SULT2B1 在食管鳞状细胞癌（ESCC）中的作用。
在 ESCC 队列中评估 SULT2B1 的表达及其临床病理特征。使用亚硫酸氢盐基因组测序和甲基化特异性 PCR 检测 SULT2B1 基因启动子的高甲基化。通过功能测定鉴定 SULT2B1 对 ESCC 细胞生物学特性的影响。皮下异种移植模型揭示了 SULT2B1 在体内对肿瘤生长的作用。进行 RNA-Seq 分析和 qRT-PCR 以识别 SULT2B1 对 PER1 的靶向作用。
大多数 ESCC 患者或 ESCC 细胞系中 SULT2B1 不表达或低表达，且伴有不良的临床预后。此外，SULT2B1 的下调发生在启动子甲基化中。根据功能结果，SULT2B1 的过表达可抑制体外肿瘤增殖并延缓体内肿瘤生长，而 SULT2B1 的敲低可加速 ESCC 进展。在转录后调控过程中，SULT2B1 靶向 PER1 的 mRNA 水平。最后，PER1 被验证为 ESCC 的抑制因子和预后不良因素。
SULT2B1 的缺失是由于其促进甲基化的能力所致。此外，它作为一种抑制因子和预后不良因素，是因为 SULT2B1 在 ESCC 中对 PER1 的转录后调控。
