The promoter hypermethylation of SULT2B1 accelerates esophagus tumorigenesis via downregulated PER1

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.

Mechanisms of radiotherapy resistance and radiosensitization strategies for esophageal squamous cell carcinoma

“…This affects the ability of DNA to coil around histones and results in a condensed heterochromatin conformation, which prevents genes from being transcribed [ 148 ]. High promoter methylation of ESCC suppressor genes, such as p16 [ 149 ], RASSF5A [ 150 ], SULT2B1 [ 151 ], SEMA3B [ 152 ], PTPN6 [ 153 ] and Bin1 [ 154 ] can lead to tumor suppressor gene silencing and cancer cell activation and can be used as a predictor of clinical outcome after radical resection in ESCC patients. Aberrant DNA methylation contributes to the development of radioresistance during anticancer therapy; for example, high methylation of death-associated protein kinase (DAPK) [ 155 ], CHFR [ 156 ] and FGF5 [ 157 ] is associated with a diminished response to CRT in ESCC, in which DNA methyltransferases (DNMTs) play an important role, including DNMT1, DNMT3A and DNMT3B.…”

The Advances in Epigenetics for Cancer Radiotherapy

“…Increasing evidence shows that DNA methylation is closely related to the occurrence and development of cancers [ 11 ]. CpG islands are located in the promoter region and transcriptional initiation site of the gene, which are prone to DNA methylation and change the expression of oncogenes and tumor suppressor genes [ 12 ]. In the development of cancer, the methylation of specific gene promoter is considered to be a predictor of radiosensitivity and a prognostic factor.…”

“…The increase in UHRF1 in cervical cancer (CC) tissue promotes the hypermethylation of the TXNIP promoter to downregulate the expression of TXNIP, thus promoting carcinogenesis ( Figure 2 a) [ 18 ]. SULT2B1 can inhibit the proliferation of esophageal squamous cell carcinoma (ESCC) cells, and the hypermethylation of its promoter can promote the progression of esophageal tumor by downregulating PER1 ( Figure 2 a) [ 12 ].…”

Sulfotransferase SULT2B1 facilitates colon cancer metastasis by promoting SCD1‐mediated lipid metabolism

“…In the process of sulfate conjugation, sulfotransferase enzymes are crucial participants, facilitating the conjugation of hormones, neurotransmitters, drugs and xenobiotic compounds 20 . SULT2B1, a member of the sulfotransferase family, also referred to as sulfotransferase family 2B member 1, has been associated with the progression of multiple cancer types, including prostate cancer, 21 gastric cancer 22 and oesophagus cancer 23 . Recent research has suggested that high expression of SULT2B1 could potentially accelerate the progression of liver cancer by impacting the tumour microenvironment 24 .…”

“… 20 SULT2B1, a member of the sulfotransferase family, also referred to as sulfotransferase family 2B member 1, has been associated with the progression of multiple cancer types, including prostate cancer, 21 gastric cancer 22 and oesophagus cancer. 23 Recent research has suggested that high expression of SULT2B1 could potentially accelerate the progression of liver cancer by impacting the tumour microenvironment. 24 Nevertheless, the effect of SULT2B1‐mediated lipid metabolism on the progression of CC remains unclear.…”