The promoter hypermethylation of SULT2B1 accelerates esophagus tumorigenesis via downregulated PER1

Autor: Zhuo Li, Meng‐Yan Li, Ling‐Ling Wang, Lei Li, Qing‐Yun Chen, Ying‐Hui Zhu, Yan Li, Yan‐ru Qin, Xin‐Yuan Guan
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Thoracic Cancer, Vol 12, Iss 24, Pp 3370-3379 (2021)
Druh dokumentu: article
ISSN: 1759-7714
1759-7706
DOI: 10.1111/1759-7714.14211
Popis: Abstract Background 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). Methods 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. Results 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. Conclusions 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.
Databáze: Directory of Open Access Journals
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